Pejnović, Nada

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orcid::0000-0002-2279-9197
  • Pejnović, Nada (24)
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Author's Bibliography

Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut

Jonić, Natalija; Chatzigiannis, Christos M.; Koprivica, Ivan; Marinho, Sergio; Moura-Alves, Pedro; Pavić, Aleksandar; Otašević, Vesna; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana D.

(Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 2023)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6295
AB  - Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6295
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6295"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295
Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .

Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity

Jonić, Natalija; Chatzigiannis, Christos M.; Koprivica, Ivan; Marinho, Sergio; Moura-Alves, Pedro; Pavić, Aleksandar; Otašević, Vesna; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana D.

(European Federation of Immunological Societies (EFIS), 2023)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6296
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.
PB  - European Federation of Immunological Societies (EFIS)
C3  - Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
T1  - Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6296
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.",
publisher = "European Federation of Immunological Societies (EFIS)",
journal = "Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia",
title = "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6296"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
European Federation of Immunological Societies (EFIS)., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296
Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia. 2023;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity" in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia (2023):17,
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa

Jonić, Natalija; Chatzigiannis, Christos M; Koprivica, Ivan; Marinho, Sérgio; Moura-Alves, Pedro; Pavić, Aleksandar; Dimitrijević, Mirjana; Jovanović, Anđelina; Jovanović, Milan B; Otašević, Vesna; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana D.

(Belgrade: Serbian Academy of Sciences and Arts, 2023)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M
AU  - Koprivica, Ivan
AU  - Marinho, Sérgio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Dimitrijević, Mirjana
AU  - Jovanović, Anđelina
AU  - Jovanović, Milan B
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5731
AB  - Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
T1  - Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5731
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Dimitrijević, Mirjana and Jovanović, Anđelina and Jovanović, Milan B and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia",
title = "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5731"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5731
Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Dimitrijević M, Jovanović A, Jovanović MB, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .
Jonić, Natalija, Chatzigiannis, Christos M, Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Dimitrijević, Mirjana, Jovanović, Anđelina, Jovanović, Milan B, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa" in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .

Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine

Saksida, Tamara; Paunović, Verica; Koprivica, Ivan; Mićanović, Dragica; Jevtić, Bojan; Jonić, Natalija; Stojanović, Ivana D.; Pejnović, Nada

(MDPI, 2023)

TY  - JOUR
AU  - Saksida, Tamara
AU  - Paunović, Verica
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Jevtić, Bojan
AU  - Jonić, Natalija
AU  - Stojanović, Ivana D.
AU  - Pejnović, Nada
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5557
AB  - Recent data indicate the link between the number and function of T regulatory cells (Treg)
in the gut immune tissue and initiation and development of autoimmunity associated with type
1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for
maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis,
the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic
NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria
(SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-
induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3
and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with
broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence
of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and
FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that
the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes
progression and severity.
PB  - MDPI
PB  - Basel: MDPI
T2  - Molecules
T1  - Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine
IS  - 8
VL  - 28
DO  - 10.3390/molecules28083366
SP  - 3366
ER  - 
@article{
author = "Saksida, Tamara and Paunović, Verica and Koprivica, Ivan and Mićanović, Dragica and Jevtić, Bojan and Jonić, Natalija and Stojanović, Ivana D. and Pejnović, Nada",
year = "2023",
abstract = "Recent data indicate the link between the number and function of T regulatory cells (Treg)
in the gut immune tissue and initiation and development of autoimmunity associated with type
1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for
maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis,
the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic
NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria
(SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-
induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3
and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with
broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence
of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and
FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that
the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes
progression and severity.",
publisher = "MDPI, Basel: MDPI",
journal = "Molecules",
title = "Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine",
number = "8",
volume = "28",
doi = "10.3390/molecules28083366",
pages = "3366"
}
Saksida, T., Paunović, V., Koprivica, I., Mićanović, D., Jevtić, B., Jonić, N., Stojanović, I. D.,& Pejnović, N.. (2023). Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine. in Molecules
MDPI., 28(8), 3366.
https://doi.org/10.3390/molecules28083366
Saksida T, Paunović V, Koprivica I, Mićanović D, Jevtić B, Jonić N, Stojanović ID, Pejnović N. Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine. in Molecules. 2023;28(8):3366.
doi:10.3390/molecules28083366 .
Saksida, Tamara, Paunović, Verica, Koprivica, Ivan, Mićanović, Dragica, Jevtić, Bojan, Jonić, Natalija, Stojanović, Ivana D., Pejnović, Nada, "Development of Type 1 Diabetes in Mice Is Associated with a Decrease in IL-2-Producing ILC3 and FoxP3+ Treg in the Small Intestine" in Molecules, 28, no. 8 (2023):3366,
https://doi.org/10.3390/molecules28083366 . .
1
3
2

Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells

Mićanović, Dragica; Stojanović, Ivana D.; Koprivica, Ivan; Pejnović, Nada; Šavikin, Katarina; Ćujić-Nikolić, Nada; Saksida, Tamara

(Amsterdam : Elsevier, 2022)

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Stojanović, Ivana D.
AU  - Koprivica, Ivan
AU  - Pejnović, Nada
AU  - Šavikin, Katarina
AU  - Ćujić-Nikolić, Nada
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5021
AB  - Chokeberry has exhibited cardioprotective, anti-bacterial, immunomodulating and anti-cancer properties. Chokeberry extract (CE) was tested in the model of melanoma induced by B16 cells inoculation in C57BL/6 mice.

CE treatment that began 7 days before inoculation and continued through the observation period, delayed melanoma appearance and increased infiltration of immune cells in the tumor microenvironment (TME). Levels of TNF, perforin, granzyme B and IL-1β did not differ between the CE-treated and control animals, but the TME of CE-treated mice contained more IFN-γ-producing cells and a lesser frequency of CCR5-expressing MDSC. In vitro, CE displayed no direct cytotoxicity to B16 cells. However, splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on B16 cells in vitro. Neutralization of IFN-γ diminished the observed B16 death, suggesting that this effect was mediated mainly by splenocyte-derived IFN-γ.

In conclusion, pre-treatment with CE stimulated the anti-tumor immune response by enhancing IFN-γ-producing cells to act against melanoma.
PB  - Amsterdam : Elsevier
T2  - Journal of Functional Foods
T1  - Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells
VL  - 95
DO  - 10.1016/j.jff.2022.105185
SP  - 105185
ER  - 
@article{
author = "Mićanović, Dragica and Stojanović, Ivana D. and Koprivica, Ivan and Pejnović, Nada and Šavikin, Katarina and Ćujić-Nikolić, Nada and Saksida, Tamara",
year = "2022",
abstract = "Chokeberry has exhibited cardioprotective, anti-bacterial, immunomodulating and anti-cancer properties. Chokeberry extract (CE) was tested in the model of melanoma induced by B16 cells inoculation in C57BL/6 mice.

CE treatment that began 7 days before inoculation and continued through the observation period, delayed melanoma appearance and increased infiltration of immune cells in the tumor microenvironment (TME). Levels of TNF, perforin, granzyme B and IL-1β did not differ between the CE-treated and control animals, but the TME of CE-treated mice contained more IFN-γ-producing cells and a lesser frequency of CCR5-expressing MDSC. In vitro, CE displayed no direct cytotoxicity to B16 cells. However, splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on B16 cells in vitro. Neutralization of IFN-γ diminished the observed B16 death, suggesting that this effect was mediated mainly by splenocyte-derived IFN-γ.

In conclusion, pre-treatment with CE stimulated the anti-tumor immune response by enhancing IFN-γ-producing cells to act against melanoma.",
publisher = "Amsterdam : Elsevier",
journal = "Journal of Functional Foods",
title = "Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells",
volume = "95",
doi = "10.1016/j.jff.2022.105185",
pages = "105185"
}
Mićanović, D., Stojanović, I. D., Koprivica, I., Pejnović, N., Šavikin, K., Ćujić-Nikolić, N.,& Saksida, T.. (2022). Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells. in Journal of Functional Foods
Amsterdam : Elsevier., 95, 105185.
https://doi.org/10.1016/j.jff.2022.105185
Mićanović D, Stojanović ID, Koprivica I, Pejnović N, Šavikin K, Ćujić-Nikolić N, Saksida T. Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells. in Journal of Functional Foods. 2022;95:105185.
doi:10.1016/j.jff.2022.105185 .
Mićanović, Dragica, Stojanović, Ivana D., Koprivica, Ivan, Pejnović, Nada, Šavikin, Katarina, Ćujić-Nikolić, Nada, Saksida, Tamara, "Chokeberry (Aronia melanocarpa) fruit extract abrogates melanoma progression through boosting up IFN-γ-producing cells" in Journal of Functional Foods, 95 (2022):105185,
https://doi.org/10.1016/j.jff.2022.105185 . .
3
1

Etil-piruvat i autoimunske bolesti

Mićanović, Dragica; Nikolovski, Neda; Koprivica, Ivan; Despotović, Sanja; Jevtić, Bojan; Stanisavljević, Suzana; Momčilović, Miljana; Pejnović, Nada; Stojanović, Ivana D.; Miljković, Đorđe; Saksida, Tamara

(Belgrade: Serbian Academy of Sciences and Arts, 2022)

TY  - CONF
AU  - Mićanović, Dragica
AU  - Nikolovski, Neda
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Momčilović, Miljana
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5770
AB  - Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима.
AB  - Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
T1  - Etil-piruvat i autoimunske bolesti
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5770
ER  - 
@conference{
author = "Mićanović, Dragica and Nikolovski, Neda and Koprivica, Ivan and Despotović, Sanja and Jevtić, Bojan and Stanisavljević, Suzana and Momčilović, Miljana and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2022",
abstract = "Примена етил-пирувата у третману аутоимунских болести је испитивана
у анималним моделима дијабетеса типа 1, мултипле склерозе и
миокардитиса. Показало се да етил-пируват ефикасно делује против
аутоимунских процеса и следствено доводи до побољшања клиничке
слике у овим моделима. Као главне мете деловања овог једињења
идентификоване су дендритске ћелије и Т лимфоцити. Утврђено је да
етил пируват потенцира толерогена својства денритских ћелија, као и
регулаторне Т лимфоците, a да инхибира ефекторске функције макрофага
и ограничава активацију и функцију ефекторских Т лимфоцита.
Инхибиторно дејство етил-пирувата на аутоимунске процесе је остварено
захваљујући његовим редокс и метаболичким ефектима, а пре свега
посредством његове интеракције са молекулом ХМГБ1. Имајући у виду да
су претходна истраживања показала да је примена етил-пирувата у људи
безбедна, будућа истраживања би морала бити усмерена ка транслацији
сазнања стечених у анималним моделима на терапијску примену овог
једињења у аутоимунским болестима., Primena etil-piruvata u tretmanu autoimunskih bolesti je ispitivana u animalnim modelima dijabetesa tipa 1, multiple skleroze i miokarditisa. Pokazalo se da etil-piruvat efikasno deluje protiv autoimunskih procesa i sledstveno dovodi do poboljšanja kliničke slike u ovim modelima. Kao glavne mete delovanja ovog jedinjenja identifikovane su dendritske ćelije i T limfociti. Utvrđeno je da etil piruvat potencira tolerogena svojstva denritskih ćelija, kao i regulatorne T limfocite, a da inhibira efektorske funkcije makrofaga i ograničava aktivaciju i funkciju efektorskih T limfocita. Inhibitorno dejstvo etil-piruvata na autoimunske procese je ostvareno zahvaljujući njegovim redoks i metaboličkim efektima, a pre svega posredstvom njegove interakcije sa molekulom HMGB1. Imajući u vidu da su prethodna istraživanja pokazala da je primena etil-piruvata u ljudi bezbedna, buduća istraživanja bi morala biti usmerena ka translaciji saznanja stečenih u animalnim modelima na terapijsku primenu ovog jedinjenja u autoimunskim bolestima.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia",
title = "Etil-piruvat i autoimunske bolesti",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5770"
}
Mićanović, D., Nikolovski, N., Koprivica, I., Despotović, S., Jevtić, B., Stanisavljević, S., Momčilović, M., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2022). Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5770
Mićanović D, Nikolovski N, Koprivica I, Despotović S, Jevtić B, Stanisavljević S, Momčilović M, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Etil-piruvat i autoimunske bolesti. in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia. 2022;.
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .
Mićanović, Dragica, Nikolovski, Neda, Koprivica, Ivan, Despotović, Sanja, Jevtić, Bojan, Stanisavljević, Suzana, Momčilović, Miljana, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Etil-piruvat i autoimunske bolesti" in Naučni skup Svetski dan imunologije 2022; 2022 Apr 28; Belgrade, Serbia (2022),
https://hdl.handle.net/21.15107/rcub_ibiss_5770 .

Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice

Koprivica, Ivan; Jonić, Natalija; Diamantis, Dimitris; Mićanović, Dragica; Saksida, Tamara; Pejnović, Nada; Tzakos, Andreas G.; Stojanović, Ivana D.

(2022)

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320521011711
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4700
AB  - Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.
T2  - Life Sciences
T1  - Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice
VL  - 288
DO  - 10.1016/j.lfs.2021.120184
SP  - 120184
ER  - 
@article{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2022",
abstract = "Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.",
journal = "Life Sciences",
title = "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice",
volume = "288",
doi = "10.1016/j.lfs.2021.120184",
pages = "120184"
}
Koprivica, I., Jonić, N., Diamantis, D., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A. G.,& Stojanović, I. D.. (2022). Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences, 288, 120184.
https://doi.org/10.1016/j.lfs.2021.120184
Koprivica I, Jonić N, Diamantis D, Mićanović D, Saksida T, Pejnović N, Tzakos AG, Stojanović ID. Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences. 2022;288:120184.
doi:10.1016/j.lfs.2021.120184 .
Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas G., Stojanović, Ivana D., "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice" in Life Sciences, 288 (2022):120184,
https://doi.org/10.1016/j.lfs.2021.120184 . .
1
3
3

Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma

Mićanović, Dragica; Koprivica, Ivan; Šavikin, Katarina; Šenerović, Lidija; Despotović, Sanja; Pejnović, Nada; Stojanović, Ivana D.; Saksida, Tamara

(Belgrade: Faculty of Chemistry, 2022)

TY  - CONF
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Šavikin, Katarina
AU  - Šenerović, Lidija
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5779
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually
exhibit cardioprotective, anti-viral and anti-bacterial properties1. Our aim was to
investigate the effects of CE on the immune response in vivo and in vitro, which have been
only sporadically assessed. CE, administered orally to healthy mice, exerted
immunomodulatory effects in the gut, evidenced by the altered proportion of macrophages
(Mφ), dendritic cells (DC) and T cells. CE-pretreated BALB/c mice readily eradicated
orally ingested Listeria monocytogenes due to higher proportions of Mφ and CD8 T cells
both in the gut and spleen. Additionally, phagocytosis, ROS production and the
proportions of activated Mφ and DC, as well as perforin+ cells were enhanced in CEpretreated
infected mice. Also, CE pretreatment of C57BL/6 mice inoculated with B16
cells delayed melanoma appearance and increased infiltration of immune cells in the tumor
microenvironment (TME). The TME of CE-treated mice contained more IFN-γ+ cells and
a less of tumor-promoting CCR5+ MDSC. In vitro, CE displayed no direct cytotoxicity to
B16 cells. Splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on
B16 cells and this effect was diminished by neutralization of IFN-γ. In conclusion, the CE
exhibits strong immunomodulatory properties and should be consumed with care.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma
SP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5779
ER  - 
@conference{
author = "Mićanović, Dragica and Koprivica, Ivan and Šavikin, Katarina and Šenerović, Lidija and Despotović, Sanja and Pejnović, Nada and Stojanović, Ivana D. and Saksida, Tamara",
year = "2022",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually
exhibit cardioprotective, anti-viral and anti-bacterial properties1. Our aim was to
investigate the effects of CE on the immune response in vivo and in vitro, which have been
only sporadically assessed. CE, administered orally to healthy mice, exerted
immunomodulatory effects in the gut, evidenced by the altered proportion of macrophages
(Mφ), dendritic cells (DC) and T cells. CE-pretreated BALB/c mice readily eradicated
orally ingested Listeria monocytogenes due to higher proportions of Mφ and CD8 T cells
both in the gut and spleen. Additionally, phagocytosis, ROS production and the
proportions of activated Mφ and DC, as well as perforin+ cells were enhanced in CEpretreated
infected mice. Also, CE pretreatment of C57BL/6 mice inoculated with B16
cells delayed melanoma appearance and increased infiltration of immune cells in the tumor
microenvironment (TME). The TME of CE-treated mice contained more IFN-γ+ cells and
a less of tumor-promoting CCR5+ MDSC. In vitro, CE displayed no direct cytotoxicity to
B16 cells. Splenocytes isolated from CE-treated animals exerted strong cytotoxic effect on
B16 cells and this effect was diminished by neutralization of IFN-γ. In conclusion, the CE
exhibits strong immunomodulatory properties and should be consumed with care.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma",
pages = "98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5779"
}
Mićanović, D., Koprivica, I., Šavikin, K., Šenerović, L., Despotović, S., Pejnović, N., Stojanović, I. D.,& Saksida, T.. (2022). Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 98.
https://hdl.handle.net/21.15107/rcub_ibiss_5779
Mićanović D, Koprivica I, Šavikin K, Šenerović L, Despotović S, Pejnović N, Stojanović ID, Saksida T. Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:98.
https://hdl.handle.net/21.15107/rcub_ibiss_5779 .
Mićanović, Dragica, Koprivica, Ivan, Šavikin, Katarina, Šenerović, Lidija, Despotović, Sanja, Pejnović, Nada, Stojanović, Ivana D., Saksida, Tamara, "Effects of chokeberry fruit water extract on immune system in mouse models of infection and melanoma" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):98,
https://hdl.handle.net/21.15107/rcub_ibiss_5779 .

Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora

Mićanović, Dragica; Saksida, Tamara; Koprivica, Ivan; Vujičić, Milica; Šavikin, Katarina; Šenerović, Lidija; Despotović, Sanja; Pejnović, Nada; Stojanović, Ivana D.

(Belgrade: Serbian Academy of Sciences and Arts, 2021)

TY  - CONF
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Vujičić, Milica
AU  - Šavikin, Katarina
AU  - Šenerović, Lidija
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5769
AB  - Аронија (lat. Aronia melanocarpa), воће карактеристично по тамним
бобицама опорог укуса, садржи мноштво фенолних једињења заслужних за
антиоксидативна својства ове биљне врсте. Водени екстракт плода ароније
(ВЕПА) у овом истраживању показао је проинфламацијско дејство: in vitro
је повећао фагоцитну способност макрофага и стимулисао продукцију
азот моноксида, као и диференцијацију проинфламацијских Т лимфоцита,
а in vivo након оралне примене је повећао заступљеност ефекторских Т
лимфоцита у Пејеровим плочама, као и продукцију IFN-γ на системском
нивоу. Да би се додатно испитао проинфламацијски потенцијал ВЕПА,
коришћени су експериментални мишји модели инфекције бактеријом
Listeria monocytogenes и меланома. Показано је да претретман ВЕПА не
само умањује губитак телесне масе и помаже ерадикацију инфекције, већ
и у Пејеровим плочама и слезини доводи до повећане заступљености CD8+
Т лимфоцита и CD11b+ макрофага, који се одликују већом фагоцитном
способношћу. У моделу меланома на мишевима, након седмодневног
претретмана ВЕПА индукован је меланом поткожним давањем 2.5х105 Б16
ћелија и орални третман ВЕПА је настављен до краја експеримента. Осим
што је успорио развој тумора и његову запремину, претретман је повећао
инфилтрацију имунских ћелија у тумор, као и заступљеност IFN-γ+ ћелија
унутар NK+, CD4+ и CD8+ ћелија, док је заступљеност супресорских ћелија
смањена. Ови резултати указују на потенцијал примене ароније у превенцији
стања и болести у којима је неопходна стимулација проинфламацијског
имунског одговора.
AB  - Aronija (lat. Aronia melanocarpa), voće karakteristično po tamnim bobicama oporog ukusa, sadrži mnoštvo fenolnih jedinjenja zaslužnih za antioksidativna svojstva ove biljne vrste. Vodeni ekstrakt ploda aronije (VEPA) u ovom istraživanju pokazao je proinflamacijsko dejstvo: in vitro je povećao fagocitnu sposobnost makrofaga i stimulisao produkciju azot monoksida, kao i diferencijaciju proinflamacijskih T limfocita, a in vivo nakon oralne primene je povećao zastupljenost efektorskih T limfocita u Pejerovim pločama, kao i produkciju IFN-γ na sistemskom nivou. Da bi se dodatno ispitao proinflamacijski potencijal VEPA, korišćeni su eksperimentalni mišji modeli infekcije bakterijom Listeria monocytogenes i melanoma. Pokazano je da pretretman VEPA ne samo umanjuje gubitak telesne mase i pomaže eradikaciju infekcije, već i u Pejerovim pločama i slezini dovodi do povećane zastupljenosti CD8+ T limfocita i CD11b+ makrofaga, koji se odlikuju većom fagocitnom sposobnošću. U modelu melanoma na miševima, nakon sedmodnevnog pretretmana VEPA indukovan je melanom potkožnim davanjem 2.5h105 B16 ćelija i oralni tretman VEPA je nastavljen do kraja eksperimenta. Osim što je usporio razvoj tumora i njegovu zapreminu, pretretman je povećao infiltraciju imunskih ćelija u tumor, kao i zastupljenost IFN-γ+ ćelija unutar NK+, CD4+ i CD8+ ćelija, dok je zastupljenost supresorskih ćelija smanjena. Ovi rezultati ukazuju na potencijal primene aronije u prevenciji stanja i bolesti u kojima je neophodna stimulacija proinflamacijskog imunskog odgovora.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia
T1  - Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora
T1  - Утицај воденог екстракта плода ароније на имунски систем у мишјим моделима инфекције и тумора
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5769
ER  - 
@conference{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Vujičić, Milica and Šavikin, Katarina and Šenerović, Lidija and Despotović, Sanja and Pejnović, Nada and Stojanović, Ivana D.",
year = "2021",
abstract = "Аронија (lat. Aronia melanocarpa), воће карактеристично по тамним
бобицама опорог укуса, садржи мноштво фенолних једињења заслужних за
антиоксидативна својства ове биљне врсте. Водени екстракт плода ароније
(ВЕПА) у овом истраживању показао је проинфламацијско дејство: in vitro
је повећао фагоцитну способност макрофага и стимулисао продукцију
азот моноксида, као и диференцијацију проинфламацијских Т лимфоцита,
а in vivo након оралне примене је повећао заступљеност ефекторских Т
лимфоцита у Пејеровим плочама, као и продукцију IFN-γ на системском
нивоу. Да би се додатно испитао проинфламацијски потенцијал ВЕПА,
коришћени су експериментални мишји модели инфекције бактеријом
Listeria monocytogenes и меланома. Показано је да претретман ВЕПА не
само умањује губитак телесне масе и помаже ерадикацију инфекције, већ
и у Пејеровим плочама и слезини доводи до повећане заступљености CD8+
Т лимфоцита и CD11b+ макрофага, који се одликују већом фагоцитном
способношћу. У моделу меланома на мишевима, након седмодневног
претретмана ВЕПА индукован је меланом поткожним давањем 2.5х105 Б16
ћелија и орални третман ВЕПА је настављен до краја експеримента. Осим
што је успорио развој тумора и његову запремину, претретман је повећао
инфилтрацију имунских ћелија у тумор, као и заступљеност IFN-γ+ ћелија
унутар NK+, CD4+ и CD8+ ћелија, док је заступљеност супресорских ћелија
смањена. Ови резултати указују на потенцијал примене ароније у превенцији
стања и болести у којима је неопходна стимулација проинфламацијског
имунског одговора., Aronija (lat. Aronia melanocarpa), voće karakteristično po tamnim bobicama oporog ukusa, sadrži mnoštvo fenolnih jedinjenja zaslužnih za antioksidativna svojstva ove biljne vrste. Vodeni ekstrakt ploda aronije (VEPA) u ovom istraživanju pokazao je proinflamacijsko dejstvo: in vitro je povećao fagocitnu sposobnost makrofaga i stimulisao produkciju azot monoksida, kao i diferencijaciju proinflamacijskih T limfocita, a in vivo nakon oralne primene je povećao zastupljenost efektorskih T limfocita u Pejerovim pločama, kao i produkciju IFN-γ na sistemskom nivou. Da bi se dodatno ispitao proinflamacijski potencijal VEPA, korišćeni su eksperimentalni mišji modeli infekcije bakterijom Listeria monocytogenes i melanoma. Pokazano je da pretretman VEPA ne samo umanjuje gubitak telesne mase i pomaže eradikaciju infekcije, već i u Pejerovim pločama i slezini dovodi do povećane zastupljenosti CD8+ T limfocita i CD11b+ makrofaga, koji se odlikuju većom fagocitnom sposobnošću. U modelu melanoma na miševima, nakon sedmodnevnog pretretmana VEPA indukovan je melanom potkožnim davanjem 2.5h105 B16 ćelija i oralni tretman VEPA je nastavljen do kraja eksperimenta. Osim što je usporio razvoj tumora i njegovu zapreminu, pretretman je povećao infiltraciju imunskih ćelija u tumor, kao i zastupljenost IFN-γ+ ćelija unutar NK+, CD4+ i CD8+ ćelija, dok je zastupljenost supresorskih ćelija smanjena. Ovi rezultati ukazuju na potencijal primene aronije u prevenciji stanja i bolesti u kojima je neophodna stimulacija proinflamacijskog imunskog odgovora.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia",
title = "Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora, Утицај воденог екстракта плода ароније на имунски систем у мишјим моделима инфекције и тумора",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5769"
}
Mićanović, D., Saksida, T., Koprivica, I., Vujičić, M., Šavikin, K., Šenerović, L., Despotović, S., Pejnović, N.,& Stojanović, I. D.. (2021). Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora. in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5769
Mićanović D, Saksida T, Koprivica I, Vujičić M, Šavikin K, Šenerović L, Despotović S, Pejnović N, Stojanović ID. Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora. in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia. 2021;.
https://hdl.handle.net/21.15107/rcub_ibiss_5769 .
Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Vujičić, Milica, Šavikin, Katarina, Šenerović, Lidija, Despotović, Sanja, Pejnović, Nada, Stojanović, Ivana D., "Uticaj vodenog ekstrakta ploda aronije na imunski sistem u mišjim modelima infekcije i tumora" in Naučni skup Svetski dan imunologije 2021; 2021 Apr 29; Belgrade, Serbia (2021),
https://hdl.handle.net/21.15107/rcub_ibiss_5769 .

ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice

Koprivica, Ivan; Mićanović, Dragica; Saksida, Tamara; Cavalli, Eugenio; Auci, Dominick; Despotović, Sanja; Pejnović, Nada; Stošić-Grujičić, Stanislava; Nicoletti, Ferdinando; Stojanović, Ivana D.

(Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade, 2021)

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5781
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5781
ER  - 
@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2021",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory
response causes the death of pancreatic β-cells. Attempts to induce antiinflammatory/
regulatory immune mechanisms that would attenuate disease progression
have shown little or no beneficial effects. We introduced microparticles (MPs) loaded
with Transforming Growth Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA),
both known stimulators of T regulatory cell (Treg) differentiation and stabilization.
Male C57BL/6 mice were treated with multiple low doses of streptozotocin to induce
T1D, and orally treated with vehicle, empty MPs, or ATRA- and TGF-β-loaded MPs
for 10 days (every other day). T1D incidence and immune cell infiltration into the
pancreatic islets were lower in ATRA/TGF-β-MPs-treated mice. In Peyer’s patches
(PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β expression was reduced in PP, as was the ratio of iNOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower and was accompanied by down-regulation
in the expression of RORγt, a key transcription factor of IL-17. In the pancreatic lymph
nodes (PLN), the situation was similar to PP regarding the down-regulation of Th1
cells. Additionally, in response to ATRA/TGF-β MPs treatment, the proliferation of T
effector cells was reduced in PLN, while Treg proliferated more. The presence of
CTLA-4+PD1+ and CD39+IL-10+ Treg populations was also increased, indicating
higher suppressive activity. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg and inhibition of Th1
cell differentiation in gut-associated lymphoid tissue and the draining lymph nodes,
thus blocking the entrance of immune cells into the pancreatic islets and protecting β-
cells from further destruction.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5781"
}
Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2021). ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781
Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:100.
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .
Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "ATRA- and TGF-β-loaded microparticles ameliorate type 1 diabetes in mice" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):100,
https://hdl.handle.net/21.15107/rcub_ibiss_5781 .

Ethyl pyruvate stimulates differentiation of regulatory cells in vitro and in vivo

Koprivica, Ivan; Mićanović, Dragica; Pejnović, Nada; Saksida, Tamara; Stojanović, Ivana D.

(Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade, 2021)

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Pejnović, Nada
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5780
AB  - Ethyl pyruvate (EP) is a stable form of pyruvate that has shown potent anti-oxidant and
anti-inflammatory properties both in vitro and in vivo and was able to ameliorate
systemic inflammation and multiple organ dysfunctions in multiple animal models. Our
recent study suggests that the application of EP in the mouse model of type 1 diabetes
successfully prevents the clinical manifestation of the disease by augmenting the
number of tolerogenic dendritic cells and regulatory T cells (Treg). Our present study
indicates that during in vitro differentiation of CD4+ naïve cells into Treg, the addition
of EP stimulated Treg generation. This was in line with the observed increased
proliferation of newly differentiated Treg (Ki67+FoxP3+). Surprisingly, EP did not
scavenge reactive oxygen species (ROS), but rather stimulated ROS production by
Treg. In Treg, ROS is mainly generated during oxidative phosphorylation (OXPHOS)
during which the majority of energy for the cell is produced. EP probably acted as a
substrate in Krebs cycle because the cells produced more pyruvate dehydrogenase,
which converts pyruvate to acetyl CoA. EP treatment also resulted in less kinase of
pyruvate dehydrogenase, which acts as an inhibitor of Krebs cycle. As a result, there
was an evident stimulation of OXPHOS, confirmed by increased ATP production in
differentiated Treg. Additionally, EP exerted its stimulatory function on Treg in healthy
C57BL/6 mice. When given either intraperitoneally or per os, EP increased Treg
numbers within the peritoneal cavity or gut-associated lymphoid tissue, respectively.
Seemingly, EP promoted differentiation of Treg in vivo and did not affect their
suppressive properties (proportion of CTLA-4+, CD39+, PD-1+, IL-10+ Treg) or their
affinity towards specific effector T helper cells (RORγT+, Tbet+ or GATA-3+ Treg). In
conclusion, EP acts as specific metabolic fuel for Treg generation, likely because these
cells mainly rely on OXPHOS-derived energy
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5780
ER  - 
@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Pejnović, Nada and Saksida, Tamara and Stojanović, Ivana D.",
year = "2021",
abstract = "Ethyl pyruvate (EP) is a stable form of pyruvate that has shown potent anti-oxidant and
anti-inflammatory properties both in vitro and in vivo and was able to ameliorate
systemic inflammation and multiple organ dysfunctions in multiple animal models. Our
recent study suggests that the application of EP in the mouse model of type 1 diabetes
successfully prevents the clinical manifestation of the disease by augmenting the
number of tolerogenic dendritic cells and regulatory T cells (Treg). Our present study
indicates that during in vitro differentiation of CD4+ naïve cells into Treg, the addition
of EP stimulated Treg generation. This was in line with the observed increased
proliferation of newly differentiated Treg (Ki67+FoxP3+). Surprisingly, EP did not
scavenge reactive oxygen species (ROS), but rather stimulated ROS production by
Treg. In Treg, ROS is mainly generated during oxidative phosphorylation (OXPHOS)
during which the majority of energy for the cell is produced. EP probably acted as a
substrate in Krebs cycle because the cells produced more pyruvate dehydrogenase,
which converts pyruvate to acetyl CoA. EP treatment also resulted in less kinase of
pyruvate dehydrogenase, which acts as an inhibitor of Krebs cycle. As a result, there
was an evident stimulation of OXPHOS, confirmed by increased ATP production in
differentiated Treg. Additionally, EP exerted its stimulatory function on Treg in healthy
C57BL/6 mice. When given either intraperitoneally or per os, EP increased Treg
numbers within the peritoneal cavity or gut-associated lymphoid tissue, respectively.
Seemingly, EP promoted differentiation of Treg in vivo and did not affect their
suppressive properties (proportion of CTLA-4+, CD39+, PD-1+, IL-10+ Treg) or their
affinity towards specific effector T helper cells (RORγT+, Tbet+ or GATA-3+ Treg). In
conclusion, EP acts as specific metabolic fuel for Treg generation, likely because these
cells mainly rely on OXPHOS-derived energy",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5780"
}
Koprivica, I., Mićanović, D., Pejnović, N., Saksida, T.,& Stojanović, I. D.. (2021). Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 8.
https://hdl.handle.net/21.15107/rcub_ibiss_5780
Koprivica I, Mićanović D, Pejnović N, Saksida T, Stojanović ID. Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2021;:8.
https://hdl.handle.net/21.15107/rcub_ibiss_5780 .
Koprivica, Ivan, Mićanović, Dragica, Pejnović, Nada, Saksida, Tamara, Stojanović, Ivana D., "Ethyl pyruvate stimulates differentiation of regulatory  cells in vitro and in vivo" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2021):8,
https://hdl.handle.net/21.15107/rcub_ibiss_5780 .

Ethyl pyruvate ameliorates experimental autoimmune myocarditis

Mićanović, Dragica; Koprivica, Ivan; Despotović, Sanja; Jonić, Natalija; Pejnović, Nada; Stojanović, Ivana D.; Miljković, Đorđe; Saksida, Tamara

(John Wiley and Sons Inc, 2021)

TY  - CONF
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Despotović, Sanja
AU  - Jonić, Natalija
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
AU  - Miljković, Đorđe
AU  - Saksida, Tamara
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5776
AB  - Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties. Here, its effects on experimental autoimmune myocarditis (EAM) induced in mice by heart-specific myosin-alpha heavy chain peptide immunization were determined. EP was applied intraperitoneally, daily, starting with the immunization. Severity of EAM was determined by histological assessment of immune cell infiltrates into the heart at day 21 post immunization. Cells were phenotypically characterized by flow cytometry. Concentration of cytokines in cell culture supernatants and sera was determined by ELISA. EP reduced infiltration of immune cells into the heart and lessened heart inflammation. Smaller number of total immune cells, as well as of CD4+ T cells, CD11b+ and CD11c+ cells was isolated from the hearts of EP-treated mice. Reduced number of antigen-presenting cells, detected by CD11c, MHC class II, and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by CD4, IFN- and IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. The number of CD11c+, CD11c+MHC class II+, and CD11c+CD86+ cells was reduced in the spleen, as well. Lower production of IFN- and IL-17 by cells of the lymph nodes draining the site of immunization in response to the immunizing antigen was observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM. EP-based therapy for the treatment of myocarditis in humans should be investigated in the forthcoming studies.
PB  - John Wiley and Sons Inc
C3  - 6th European Congress of Immunology
T1  - Ethyl pyruvate ameliorates experimental autoimmune myocarditis
DO  - 10.1002/eji.202170200
SP  - 386
ER  - 
@conference{
author = "Mićanović, Dragica and Koprivica, Ivan and Despotović, Sanja and Jonić, Natalija and Pejnović, Nada and Stojanović, Ivana D. and Miljković, Đorđe and Saksida, Tamara",
year = "2021",
abstract = "Ethyl pyruvate (EP) has profound anti-inflammatory and immunomodulatory properties. Here, its effects on experimental autoimmune myocarditis (EAM) induced in mice by heart-specific myosin-alpha heavy chain peptide immunization were determined. EP was applied intraperitoneally, daily, starting with the immunization. Severity of EAM was determined by histological assessment of immune cell infiltrates into the heart at day 21 post immunization. Cells were phenotypically characterized by flow cytometry. Concentration of cytokines in cell culture supernatants and sera was determined by ELISA. EP reduced infiltration of immune cells into the heart and lessened heart inflammation. Smaller number of total immune cells, as well as of CD4+ T cells, CD11b+ and CD11c+ cells was isolated from the hearts of EP-treated mice. Reduced number of antigen-presenting cells, detected by CD11c, MHC class II, and CD86 antibodies, as well as of T helper (Th)1 and Th17 cells, detected by CD4, IFN- and IL-17 antibodies, was determined in mediastinal lymph nodes draining the heart, in parallel. The number of CD11c+, CD11c+MHC class II+, and CD11c+CD86+ cells was reduced in the spleen, as well. Lower production of IFN- and IL-17 by cells of the lymph nodes draining the site of immunization in response to the immunizing antigen was observed in EP-treated mice. Our results clearly imply that EP restrains autoimmunity in EAM. EP-based therapy for the treatment of myocarditis in humans should be investigated in the forthcoming studies.",
publisher = "John Wiley and Sons Inc",
journal = "6th European Congress of Immunology",
title = "Ethyl pyruvate ameliorates experimental autoimmune myocarditis",
doi = "10.1002/eji.202170200",
pages = "386"
}
Mićanović, D., Koprivica, I., Despotović, S., Jonić, N., Pejnović, N., Stojanović, I. D., Miljković, Đ.,& Saksida, T.. (2021). Ethyl pyruvate ameliorates experimental autoimmune myocarditis. in 6th European Congress of Immunology
John Wiley and Sons Inc., 386.
https://doi.org/10.1002/eji.202170200
Mićanović D, Koprivica I, Despotović S, Jonić N, Pejnović N, Stojanović ID, Miljković Đ, Saksida T. Ethyl pyruvate ameliorates experimental autoimmune myocarditis. in 6th European Congress of Immunology. 2021;:386.
doi:10.1002/eji.202170200 .
Mićanović, Dragica, Koprivica, Ivan, Despotović, Sanja, Jonić, Natalija, Pejnović, Nada, Stojanović, Ivana D., Miljković, Đorđe, Saksida, Tamara, "Ethyl pyruvate ameliorates experimental autoimmune myocarditis" in 6th European Congress of Immunology (2021):386,
https://doi.org/10.1002/eji.202170200 . .
159
3

Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor

Jonić, Natalija; Chatzigiannis, Christos M.; Koprivica, Ivan; Savić, Anisia; Mićanović, Dragica; Saksida, Tamara; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana D.

(Belgrade: Faculty of Chemistry: Serbian Biochemical Society, 2021)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savić, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5605
AB  - A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor
SP  - 69
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5605
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savić, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor",
pages = "69-70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5605"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savić, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605
Jonić N, Chatzigiannis CM, Koprivica I, Savić A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savić, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):69-70,
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .

Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype

Jonić, Natalija; Chatzigiannis, Christos M.; Koprivica, Ivan; Savic, Anisia; Mićanović, Dragica; Saksida, Tamara; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana D.

(Wiley‐VCH GmbH, 2021)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savic, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4883
AB  - Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype
DO  - 10.1002/eji.202170200
SP  - 207
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savic, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype",
doi = "10.1002/eji.202170200",
pages = "207"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savic, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 207.
https://doi.org/10.1002/eji.202170200
Jonić N, Chatzigiannis CM, Koprivica I, Savic A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:207.
doi:10.1002/eji.202170200 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savic, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):207,
https://doi.org/10.1002/eji.202170200 . .
159
3

Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice

Petrović, Ivica; Pejnović, Nada; Ljujić, Biljana; Pavlović, Slađana; Miletić Kovačević, Marina; Jeftić, IIlija; Đukić, Aleksandar; Selaković, Dragica; Draginić, Nevena; Anđić, Marijana; Jovičić, Nemanja; Lukić, Miodrag L.

(Wiley‐VCH GmbH, 2021)

TY  - CONF
AU  - Petrović, Ivica
AU  - Pejnović, Nada
AU  - Ljujić, Biljana
AU  - Pavlović, Slađana
AU  - Miletić Kovačević, Marina
AU  - Jeftić, IIlija
AU  - Đukić, Aleksandar
AU  - Selaković, Dragica
AU  - Draginić, Nevena
AU  - Anđić, Marijana
AU  - Jovičić, Nemanja
AU  - Lukić, Miodrag L.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4878
AB  - During obesity hematopoetic cells‐derived galectin 3 induces insulin resistence. While the role of galectin 3 expressed in islet invading immune cells in both type of diabetes has been studied, the importance of expression of this molecule on the target pancreatic beta cells is not defined. We have used 10‐12 weeks old C57/BL6 male mice (WT) and C57/ BL6 mice with transgenically enhanced Gal‐3 expression in pancreatic β cells (TG). Obesity was induced with 16 weeks high fat diet regime. Pancreatic beta cells were tested for susceptibility to apoptosis induced by non‐esterified fatty acids and cytokines as well as parameters of oxidative stress. The overexpression of galectin 3 increases beta cells apoptosis in HFD conditions and increases the percentage of proinflammatory F4/80+ macrophages in islets that express galectin 3 and TLR4. In isolated islets, we have shown that galectin 3 overexpression increases cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress of beta cells. Also, in pancreatic lymph nodes, macrophages were shifted towards proinflammatory TNF‐α producing phenotype. By complementary approach in vivo and in vitro, we have shown that galectin 3 overexpression facilitates beta cell damage, enhances cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress in beta cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic beta cells affects the metabolism of glucose and glycoregulation in mice on HFD, affecting the fasting glycemic values, as well as glycemia after glucose loading.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice
DO  - 10.1002/eji.202170200
SP  - 366
ER  - 
@conference{
author = "Petrović, Ivica and Pejnović, Nada and Ljujić, Biljana and Pavlović, Slađana and Miletić Kovačević, Marina and Jeftić, IIlija and Đukić, Aleksandar and Selaković, Dragica and Draginić, Nevena and Anđić, Marijana and Jovičić, Nemanja and Lukić, Miodrag L.",
year = "2021",
abstract = "During obesity hematopoetic cells‐derived galectin 3 induces insulin resistence. While the role of galectin 3 expressed in islet invading immune cells in both type of diabetes has been studied, the importance of expression of this molecule on the target pancreatic beta cells is not defined. We have used 10‐12 weeks old C57/BL6 male mice (WT) and C57/ BL6 mice with transgenically enhanced Gal‐3 expression in pancreatic β cells (TG). Obesity was induced with 16 weeks high fat diet regime. Pancreatic beta cells were tested for susceptibility to apoptosis induced by non‐esterified fatty acids and cytokines as well as parameters of oxidative stress. The overexpression of galectin 3 increases beta cells apoptosis in HFD conditions and increases the percentage of proinflammatory F4/80+ macrophages in islets that express galectin 3 and TLR4. In isolated islets, we have shown that galectin 3 overexpression increases cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress of beta cells. Also, in pancreatic lymph nodes, macrophages were shifted towards proinflammatory TNF‐α producing phenotype. By complementary approach in vivo and in vitro, we have shown that galectin 3 overexpression facilitates beta cell damage, enhances cytokine and palmitate‐triggered beta cells apoptosis and also increases NO2‐ induced oxidative stress in beta cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic beta cells affects the metabolism of glucose and glycoregulation in mice on HFD, affecting the fasting glycemic values, as well as glycemia after glucose loading.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice",
doi = "10.1002/eji.202170200",
pages = "366"
}
Petrović, I., Pejnović, N., Ljujić, B., Pavlović, S., Miletić Kovačević, M., Jeftić, I., Đukić, A., Selaković, D., Draginić, N., Anđić, M., Jovičić, N.,& Lukić, M. L.. (2021). Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 366.
https://doi.org/10.1002/eji.202170200
Petrović I, Pejnović N, Ljujić B, Pavlović S, Miletić Kovačević M, Jeftić I, Đukić A, Selaković D, Draginić N, Anđić M, Jovičić N, Lukić ML. Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:366.
doi:10.1002/eji.202170200 .
Petrović, Ivica, Pejnović, Nada, Ljujić, Biljana, Pavlović, Slađana, Miletić Kovačević, Marina, Jeftić, IIlija, Đukić, Aleksandar, Selaković, Dragica, Draginić, Nevena, Anđić, Marijana, Jovičić, Nemanja, Lukić, Miodrag L., "Overexpression of galectin 3 in pancreatic beta cells amplifies beta cell apoptosis and islet inflammation in type 2 diabetes in mice" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):366,
https://doi.org/10.1002/eji.202170200 . .
159
3

Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes.

Stojanović, Ivana D.; Saksida, Tamara; Miljković, Đorđe; Pejnović, Nada

(2021)

TY  - JOUR
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
AU  - Pejnović, Nada
PY  - 2021
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2021.653560/full
UR  - http://www.ncbi.nlm.nih.gov/pubmed/34149694
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8209467
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4411
AB  - Gut-associated lymphoid tissue (GALT) is crucial for the maintenance of the intestinal homeostasis, but it is also the potential site of the activation of autoreactive cells and initiation/propagation of autoimmune diseases in the gut and in the distant organs. Type 3 innate lymphoid cells (ILC3) residing in the GALT integrate signals from food ingredients and gut microbiota metabolites in order to control local immunoreactivity. Notably, ILC3 secrete IL-17 and GM-CSF that activate immune cells in combating potentially pathogenic microorganisms. ILC3 also produce IL-22 that potentiates the strength and integrity of epithelial tight junctions, production of mucus and antimicrobial peptides thus enabling the proper function of the intestinal barrier. The newly discovered function of small intestine ILC3 is the secretion of IL-2 and the promotion of regulatory T cell (Treg) generation and function. Since the intestinal barrier dysfunction, together with the reduction in small intestine ILC3 and Treg numbers are associated with the pathogenesis of type 1 diabetes (T1D), the focus of this article is intestinal ILC3 modulation for the therapy of T1D. Of particular interest is free fatty acids receptor 2 (FFAR2), predominantly expressed on intestinal ILC3, that can be stimulated by available selective synthetic agonists. Thus, we propose that FFAR2-based interventions by boosting ILC3 beneficial functions may attenuate autoimmune response against pancreatic β cells during T1D. Also, it is our opinion that treatments based on ILC3 stimulation by functional foods can be used as prophylaxis in individuals that are genetically predisposed to develop T1D.
T2  - Frontiers in Immunology
T1  - Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes.
VL  - 12
DO  - 10.3389/fimmu.2021.653560
SP  - 653560
ER  - 
@article{
author = "Stojanović, Ivana D. and Saksida, Tamara and Miljković, Đorđe and Pejnović, Nada",
year = "2021",
abstract = "Gut-associated lymphoid tissue (GALT) is crucial for the maintenance of the intestinal homeostasis, but it is also the potential site of the activation of autoreactive cells and initiation/propagation of autoimmune diseases in the gut and in the distant organs. Type 3 innate lymphoid cells (ILC3) residing in the GALT integrate signals from food ingredients and gut microbiota metabolites in order to control local immunoreactivity. Notably, ILC3 secrete IL-17 and GM-CSF that activate immune cells in combating potentially pathogenic microorganisms. ILC3 also produce IL-22 that potentiates the strength and integrity of epithelial tight junctions, production of mucus and antimicrobial peptides thus enabling the proper function of the intestinal barrier. The newly discovered function of small intestine ILC3 is the secretion of IL-2 and the promotion of regulatory T cell (Treg) generation and function. Since the intestinal barrier dysfunction, together with the reduction in small intestine ILC3 and Treg numbers are associated with the pathogenesis of type 1 diabetes (T1D), the focus of this article is intestinal ILC3 modulation for the therapy of T1D. Of particular interest is free fatty acids receptor 2 (FFAR2), predominantly expressed on intestinal ILC3, that can be stimulated by available selective synthetic agonists. Thus, we propose that FFAR2-based interventions by boosting ILC3 beneficial functions may attenuate autoimmune response against pancreatic β cells during T1D. Also, it is our opinion that treatments based on ILC3 stimulation by functional foods can be used as prophylaxis in individuals that are genetically predisposed to develop T1D.",
journal = "Frontiers in Immunology",
title = "Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes.",
volume = "12",
doi = "10.3389/fimmu.2021.653560",
pages = "653560"
}
Stojanović, I. D., Saksida, T., Miljković, Đ.,& Pejnović, N.. (2021). Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes.. in Frontiers in Immunology, 12, 653560.
https://doi.org/10.3389/fimmu.2021.653560
Stojanović ID, Saksida T, Miljković Đ, Pejnović N. Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes.. in Frontiers in Immunology. 2021;12:653560.
doi:10.3389/fimmu.2021.653560 .
Stojanović, Ivana D., Saksida, Tamara, Miljković, Đorđe, Pejnović, Nada, "Modulation of Intestinal ILC3 for the Treatment of Type 1 Diabetes." in Frontiers in Immunology, 12 (2021):653560,
https://doi.org/10.3389/fimmu.2021.653560 . .
2
9
2
7

Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.

Jovičić, Nemanja; Petrović, Ivica; Pejnović, Nada; Ljujić, Biljana; Miletić Kovačević, Marina; Pavlović, Slađana; Jeftić, Ilija; Đukić, Aleksandar; Srejović, Ivan; Jakovljević, Vladimir; Lukić, Miodrag L.

(Lausanne: Frontiers Media S.A., 2021)

TY  - JOUR
AU  - Jovičić, Nemanja
AU  - Petrović, Ivica
AU  - Pejnović, Nada
AU  - Ljujić, Biljana
AU  - Miletić Kovačević, Marina
AU  - Pavlović, Slađana
AU  - Jeftić, Ilija
AU  - Đukić, Aleksandar
AU  - Srejović, Ivan
AU  - Jakovljević, Vladimir
AU  - Lukić, Miodrag L.
PY  - 2021
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2021.714683/full
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4697
AB  - Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD-STZ)-induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD-STZ-induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD-STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12-18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.
PB  - Lausanne: Frontiers Media S.A.
T2  - Frontiers in Pharmacology
T1  - Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.
VL  - 12
DO  - 10.3389/fphar.2021.714683
SP  - 714683
ER  - 
@article{
author = "Jovičić, Nemanja and Petrović, Ivica and Pejnović, Nada and Ljujić, Biljana and Miletić Kovačević, Marina and Pavlović, Slađana and Jeftić, Ilija and Đukić, Aleksandar and Srejović, Ivan and Jakovljević, Vladimir and Lukić, Miodrag L.",
year = "2021",
abstract = "Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD-STZ)-induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD-STZ-induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD-STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12-18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.",
publisher = "Lausanne: Frontiers Media S.A.",
journal = "Frontiers in Pharmacology",
title = "Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.",
volume = "12",
doi = "10.3389/fphar.2021.714683",
pages = "714683"
}
Jovičić, N., Petrović, I., Pejnović, N., Ljujić, B., Miletić Kovačević, M., Pavlović, S., Jeftić, I., Đukić, A., Srejović, I., Jakovljević, V.,& Lukić, M. L.. (2021). Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.. in Frontiers in Pharmacology
Lausanne: Frontiers Media S.A.., 12, 714683.
https://doi.org/10.3389/fphar.2021.714683
Jovičić N, Petrović I, Pejnović N, Ljujić B, Miletić Kovačević M, Pavlović S, Jeftić I, Đukić A, Srejović I, Jakovljević V, Lukić ML. Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.. in Frontiers in Pharmacology. 2021;12:714683.
doi:10.3389/fphar.2021.714683 .
Jovičić, Nemanja, Petrović, Ivica, Pejnović, Nada, Ljujić, Biljana, Miletić Kovačević, Marina, Pavlović, Slađana, Jeftić, Ilija, Đukić, Aleksandar, Srejović, Ivan, Jakovljević, Vladimir, Lukić, Miodrag L., "Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33." in Frontiers in Pharmacology, 12 (2021):714683,
https://doi.org/10.3389/fphar.2021.714683 . .
1
3
1

Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.

Jovičić, Nemanja; Petrović, Ivica; Pejnović, Nada; Ljujić, Biljana; Miletić Kovačević, Marina; Pavlović, Slađana; Jeftić, Ilija; Đukić, Aleksandar; Srejović, Ivan; Selaković, Dragica; Jakovljević, Vladimir; Lukić, Miodrag L.

(Wiley‐VCH GmbH, 2021)

TY  - CONF
AU  - Jovičić, Nemanja
AU  - Petrović, Ivica
AU  - Pejnović, Nada
AU  - Ljujić, Biljana
AU  - Miletić Kovačević, Marina
AU  - Pavlović, Slađana
AU  - Jeftić, Ilija
AU  - Đukić, Aleksandar
AU  - Srejović, Ivan
AU  - Selaković, Dragica
AU  - Jakovljević, Vladimir
AU  - Lukić, Miodrag L.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4880
AB  - Galectin 3 (gal 3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that galectin 3 plays a role in both, type 1 and type 2 diabetes. While the role of Gal‐3 expression in immune cells in experimental type 1 diabetes has been already studied, the importance of the overexpression of Gal‐3 in the target β cells is not defined. We used 10‐12 weeks old C57/BL6 male mice (WT) and C57/BL6 mice with transgenically enhanced Gal‐3 expression in pancreatic β cells (TG). Both groups, received STZ for 5 consecutive days at a dose of 40 mg/kg ip. Mice received exogenous mouse IL‐33 (0.4 μg/injection) i.p., 12th, 14 th, 16 th, and 18 th day after the disease induction. Control animals were treated with intraperitoneally PBS + citrate buffer or IL‐33 + citrate buffer. The overexpression of Gal‐3 protected β cells from apoptosis and attenuated MLD‐STZ induced hyperglycemia, glycosuria and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal‐ 3 overexpression significantly decreased the number of proinflammatory cells without affecting T regulatory cells. The application of exogenous IL‐33, attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, and competely abrogate diabetogenesis. We demonstrated the potential synergistic effect of exogenous IL‐33 and TG overexpression of Gal‐3 in β cells Not only enhanced expresion of Gal‐3 in β cells reduced T cell mediated autoimmune inflammatory disease, but also exogenous IL‐33 application had powerful terapeutic effect in TG mice.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.
DO  - 10.1002/eji.202170200
SP  - 378
ER  - 
@conference{
author = "Jovičić, Nemanja and Petrović, Ivica and Pejnović, Nada and Ljujić, Biljana and Miletić Kovačević, Marina and Pavlović, Slađana and Jeftić, Ilija and Đukić, Aleksandar and Srejović, Ivan and Selaković, Dragica and Jakovljević, Vladimir and Lukić, Miodrag L.",
year = "2021",
abstract = "Galectin 3 (gal 3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that galectin 3 plays a role in both, type 1 and type 2 diabetes. While the role of Gal‐3 expression in immune cells in experimental type 1 diabetes has been already studied, the importance of the overexpression of Gal‐3 in the target β cells is not defined. We used 10‐12 weeks old C57/BL6 male mice (WT) and C57/BL6 mice with transgenically enhanced Gal‐3 expression in pancreatic β cells (TG). Both groups, received STZ for 5 consecutive days at a dose of 40 mg/kg ip. Mice received exogenous mouse IL‐33 (0.4 μg/injection) i.p., 12th, 14 th, 16 th, and 18 th day after the disease induction. Control animals were treated with intraperitoneally PBS + citrate buffer or IL‐33 + citrate buffer. The overexpression of Gal‐3 protected β cells from apoptosis and attenuated MLD‐STZ induced hyperglycemia, glycosuria and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal‐ 3 overexpression significantly decreased the number of proinflammatory cells without affecting T regulatory cells. The application of exogenous IL‐33, attenuates the development of disease, by increasing the presence of regulatory FoxP3+ ST2+ cells, and competely abrogate diabetogenesis. We demonstrated the potential synergistic effect of exogenous IL‐33 and TG overexpression of Gal‐3 in β cells Not only enhanced expresion of Gal‐3 in β cells reduced T cell mediated autoimmune inflammatory disease, but also exogenous IL‐33 application had powerful terapeutic effect in TG mice.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.",
doi = "10.1002/eji.202170200",
pages = "378"
}
Jovičić, N., Petrović, I., Pejnović, N., Ljujić, B., Miletić Kovačević, M., Pavlović, S., Jeftić, I., Đukić, A., Srejović, I., Selaković, D., Jakovljević, V.,& Lukić, M. L.. (2021). Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 378.
https://doi.org/10.1002/eji.202170200
Jovičić N, Petrović I, Pejnović N, Ljujić B, Miletić Kovačević M, Pavlović S, Jeftić I, Đukić A, Srejović I, Selaković D, Jakovljević V, Lukić ML. Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33.. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:378.
doi:10.1002/eji.202170200 .
Jovičić, Nemanja, Petrović, Ivica, Pejnović, Nada, Ljujić, Biljana, Miletić Kovačević, Marina, Pavlović, Slađana, Jeftić, Ilija, Đukić, Aleksandar, Srejović, Ivan, Selaković, Dragica, Jakovljević, Vladimir, Lukić, Miodrag L., "Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33." in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):378,
https://doi.org/10.1002/eji.202170200 . .
159
3

Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice

Mićanović, Dragica; Saksida, Tamara; Koprivica, Ivan; Šenerović, Lidija; Morić, Ivana; Šavikin, Katarina; Menković, Nebojša; Pejnović, Nada; Stojanović, Ivana D.

(United Kingdom : Royal Society of Chemistry, 2020)

TY  - JOUR
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Koprivica, Ivan
AU  - Šenerović, Lidija
AU  - Morić, Ivana
AU  - Šavikin, Katarina
AU  - Menković, Nebojša
AU  - Pejnović, Nada
AU  - Stojanović, Ivana D.
PY  - 2020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3834
AB  - Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.
PB  - United Kingdom : Royal Society of Chemistry
T2  - Food and Function
T1  - Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice
IS  - 9
VL  - 11
DO  - 10.1039/D0FO00946F
SP  - 7793
EP  - 7803
ER  - 
@article{
author = "Mićanović, Dragica and Saksida, Tamara and Koprivica, Ivan and Šenerović, Lidija and Morić, Ivana and Šavikin, Katarina and Menković, Nebojša and Pejnović, Nada and Stojanović, Ivana D.",
year = "2020",
abstract = "Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c+ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8+ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86+ macrophages (CD11b+) and dendritic cells (CD11c+) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.",
publisher = "United Kingdom : Royal Society of Chemistry",
journal = "Food and Function",
title = "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice",
number = "9",
volume = "11",
doi = "10.1039/D0FO00946F",
pages = "7793-7803"
}
Mićanović, D., Saksida, T., Koprivica, I., Šenerović, L., Morić, I., Šavikin, K., Menković, N., Pejnović, N.,& Stojanović, I. D.. (2020). Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function
United Kingdom : Royal Society of Chemistry., 11(9), 7793-7803.
https://doi.org/10.1039/D0FO00946F
Mićanović D, Saksida T, Koprivica I, Šenerović L, Morić I, Šavikin K, Menković N, Pejnović N, Stojanović ID. Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice. in Food and Function. 2020;11(9):7793-7803.
doi:10.1039/D0FO00946F .
Mićanović, Dragica, Saksida, Tamara, Koprivica, Ivan, Šenerović, Lidija, Morić, Ivana, Šavikin, Katarina, Menković, Nebojša, Pejnović, Nada, Stojanović, Ivana D., "Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice" in Food and Function, 11, no. 9 (2020):7793-7803,
https://doi.org/10.1039/D0FO00946F . .
1
5
6

Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis.

Koprivica, Ivan; Mićanović, Dragica; Pejnović, Nada; Paunović, Verica; Saksida, Tamara; Stojanović, Ivana D.

(MDPI AG, 2020)

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Pejnović, Nada
AU  - Paunović, Verica
AU  - Saksida, Tamara
AU  - Stojanović, Ivana D.
PY  - 2020
UR  - https://www.mdpi.com/1420-3049/25/18/4112
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32916780
UR  - https://radar.ibiss.bg.ac.rs/123456789/3892
AB  - Ethyl pyruvate (EP), a stable form of pyruvate, has shown beneficial effects in animal models of shock, ischemia/reperfusion injury, and sepsis due to its potent anti-oxidant and anti-inflammatory properties. Our recent study demonstrated that EP application prevented the clinical manifestation of type 1 diabetes in mice by augmenting regulatory T cell (Treg) number and function. Our present study shows that EP increases Treg proliferation and suppressive function (perforin and IL-10 expression) during in vitro differentiation from conventional CD4+CD25- T cells. Enhanced expansion of Treg after EP treatment correlated with increased ATP levels and relied on increased glycolysis. Inhibition of oxidative phosphorylation did not attenuate EP stimulatory effects, suggesting that this metabolic pathway was not mandatory for EP-driven Treg proliferation. Moreover, EP lowered the expression of carnitine palmitoyltransferase I, an enzyme involved in fatty acid oxidation. Further, the stimulatory effect of EP on Treg proliferation was not mediated through inhibition of the mTOR signaling pathway. When given in vivo either intraperitoneally or orally to healthy C57BL/6 mice, EP increased the number of Treg within the peritoneal cavity or gut-associated lymphoid tissue, respectively. In conclusion, EP promotes in vitro Treg proliferation through increased glycolysis and enhances Treg proliferation when administered in vivo.
PB  - MDPI AG
T2  - Molecules (Basel, Switzerland)
T1  - Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis.
IS  - 18
VL  - 25
DO  - 10.3390/molecules25184112
SP  - 4112
ER  - 
@article{
author = "Koprivica, Ivan and Mićanović, Dragica and Pejnović, Nada and Paunović, Verica and Saksida, Tamara and Stojanović, Ivana D.",
year = "2020",
abstract = "Ethyl pyruvate (EP), a stable form of pyruvate, has shown beneficial effects in animal models of shock, ischemia/reperfusion injury, and sepsis due to its potent anti-oxidant and anti-inflammatory properties. Our recent study demonstrated that EP application prevented the clinical manifestation of type 1 diabetes in mice by augmenting regulatory T cell (Treg) number and function. Our present study shows that EP increases Treg proliferation and suppressive function (perforin and IL-10 expression) during in vitro differentiation from conventional CD4+CD25- T cells. Enhanced expansion of Treg after EP treatment correlated with increased ATP levels and relied on increased glycolysis. Inhibition of oxidative phosphorylation did not attenuate EP stimulatory effects, suggesting that this metabolic pathway was not mandatory for EP-driven Treg proliferation. Moreover, EP lowered the expression of carnitine palmitoyltransferase I, an enzyme involved in fatty acid oxidation. Further, the stimulatory effect of EP on Treg proliferation was not mediated through inhibition of the mTOR signaling pathway. When given in vivo either intraperitoneally or orally to healthy C57BL/6 mice, EP increased the number of Treg within the peritoneal cavity or gut-associated lymphoid tissue, respectively. In conclusion, EP promotes in vitro Treg proliferation through increased glycolysis and enhances Treg proliferation when administered in vivo.",
publisher = "MDPI AG",
journal = "Molecules (Basel, Switzerland)",
title = "Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis.",
number = "18",
volume = "25",
doi = "10.3390/molecules25184112",
pages = "4112"
}
Koprivica, I., Mićanović, D., Pejnović, N., Paunović, V., Saksida, T.,& Stojanović, I. D.. (2020). Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis.. in Molecules (Basel, Switzerland)
MDPI AG., 25(18), 4112.
https://doi.org/10.3390/molecules25184112
Koprivica I, Mićanović D, Pejnović N, Paunović V, Saksida T, Stojanović ID. Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis.. in Molecules (Basel, Switzerland). 2020;25(18):4112.
doi:10.3390/molecules25184112 .
Koprivica, Ivan, Mićanović, Dragica, Pejnović, Nada, Paunović, Verica, Saksida, Tamara, Stojanović, Ivana D., "Ethyl Pyruvate Promotes Proliferation of Regulatory T Cells by Increasing Glycolysis." in Molecules (Basel, Switzerland), 25, no. 18 (2020):4112,
https://doi.org/10.3390/molecules25184112 . .
7
6

The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice

Jevtić, Bojan; Saksida, Tamara; Mićanović, Dragica; Koprivica, Ivan; Paunović, Verica; Stojanović, Ivana D.; Pejnović, Nada

(Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade, 2019)

TY  - CONF
AU  - Jevtić, Bojan
AU  - Saksida, Tamara
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Paunović, Verica
AU  - Stojanović, Ivana D.
AU  - Pejnović, Nada
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5782
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the imbalance
between the CD4 or CD8 T effector (Teff) cells and the FoxP3+CD4 T regulatory cells
(Tregs) that leads to pancreatic beta-cells destruction causing insulin deficiency.
Environmental factors, diet and microbiome are associated with the recent rise in T1D
incidence. Intestinal immune cells must maintain a tolerogenic response in the gut that
involves the development of Tregs. Recent data show that IL-2-producing type 3 innate
lymphoid cells ILC3s (IL-2+ILC3) in the small intestine are essential for maintaining
FoxP3+ Tregs and oral tolerance to dietary antigens and reveal the previously unknown
direct communication between ILC3s and Treg cells in the gut. We investigated the
frequencies of small intestine lamina propria IL-2+ILC3s and FoxP3+ Tregs during
transition from prediabetes to diabetes in young and old female NOD mice. 20 weeks
old, diabetic NOD mice had higher frequencies of LinnegCD45+RORγt+CD127+ ILC3s
in small intestine lamina propria compared to 4 weeks of age-young NOD mice.
However, the frequencies of IL-2-producing ILC3s and CD4+CD25hiFoxP3+ Tregs
were significantly lower in diabetic NOD mice compared to young, prediabetic mice.
We next investigated how microbiota change before diabetes induction is reflected on
Treg and ILC3 populations. Male C57BL/6 mice were treated with broad spectrum
antibiotics (ABX) for 14 days and then T1D was induced by multiple low doses of
streptozotocin (STZ). Ex vivo cell analyses was done on day 10 after the first STZ
injection. The significantly higher incidence of T1D observed in ABX-treated mice
correlated with significantly lower frequencies of IL-2-producing ILC3s and
FoxP3+Tregs in small intestine lamina propria compared to mice treated with STZ only.
The obtained findings show that the decrease of tolerogenic ILC3s and FoxP3+Tregs in
small intestine is associated with the progression and higher incidence of T1D.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice
SP  - 102
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5782
ER  - 
@conference{
author = "Jevtić, Bojan and Saksida, Tamara and Mićanović, Dragica and Koprivica, Ivan and Paunović, Verica and Stojanović, Ivana D. and Pejnović, Nada",
year = "2019",
abstract = "Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the imbalance
between the CD4 or CD8 T effector (Teff) cells and the FoxP3+CD4 T regulatory cells
(Tregs) that leads to pancreatic beta-cells destruction causing insulin deficiency.
Environmental factors, diet and microbiome are associated with the recent rise in T1D
incidence. Intestinal immune cells must maintain a tolerogenic response in the gut that
involves the development of Tregs. Recent data show that IL-2-producing type 3 innate
lymphoid cells ILC3s (IL-2+ILC3) in the small intestine are essential for maintaining
FoxP3+ Tregs and oral tolerance to dietary antigens and reveal the previously unknown
direct communication between ILC3s and Treg cells in the gut. We investigated the
frequencies of small intestine lamina propria IL-2+ILC3s and FoxP3+ Tregs during
transition from prediabetes to diabetes in young and old female NOD mice. 20 weeks
old, diabetic NOD mice had higher frequencies of LinnegCD45+RORγt+CD127+ ILC3s
in small intestine lamina propria compared to 4 weeks of age-young NOD mice.
However, the frequencies of IL-2-producing ILC3s and CD4+CD25hiFoxP3+ Tregs
were significantly lower in diabetic NOD mice compared to young, prediabetic mice.
We next investigated how microbiota change before diabetes induction is reflected on
Treg and ILC3 populations. Male C57BL/6 mice were treated with broad spectrum
antibiotics (ABX) for 14 days and then T1D was induced by multiple low doses of
streptozotocin (STZ). Ex vivo cell analyses was done on day 10 after the first STZ
injection. The significantly higher incidence of T1D observed in ABX-treated mice
correlated with significantly lower frequencies of IL-2-producing ILC3s and
FoxP3+Tregs in small intestine lamina propria compared to mice treated with STZ only.
The obtained findings show that the decrease of tolerogenic ILC3s and FoxP3+Tregs in
small intestine is associated with the progression and higher incidence of T1D.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice",
pages = "102",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5782"
}
Jevtić, B., Saksida, T., Mićanović, D., Koprivica, I., Paunović, V., Stojanović, I. D.,& Pejnović, N.. (2019). The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 102.
https://hdl.handle.net/21.15107/rcub_ibiss_5782
Jevtić B, Saksida T, Mićanović D, Koprivica I, Paunović V, Stojanović ID, Pejnović N. The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:102.
https://hdl.handle.net/21.15107/rcub_ibiss_5782 .
Jevtić, Bojan, Saksida, Tamara, Mićanović, Dragica, Koprivica, Ivan, Paunović, Verica, Stojanović, Ivana D., Pejnović, Nada, "The decrease of tolerogenic ILC3 and Treg cells in small intestine corelates with the profression of type 1 diabetes in mice" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):102,
https://hdl.handle.net/21.15107/rcub_ibiss_5782 .

Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles

Koprivica, Ivan; Mićanović, Dragica; Saksida, Tamara; Cavalli, Eugenio; Auci, Dominick; Despotović, Sanja; Pejnović, Nada; Stošić-Grujičić, Stanislava; Nicoletti, Ferdinando; Stojanović, Ivana D.

(Belgrade: Faculty of Chemistry, 2019)

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5778
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.
PB  - Belgrade: Faculty of Chemistry
C3  - The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
T1  - Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5778
ER  - 
@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease in which a strong inflammatory response
causes the death of pancreatic β-cells. Attempts to induce anti-inflammatory/regulatory
immune mechanisms that would attenuate disease progression have shown little or no
beneficial effects. We introduced microparticles (MPs) loaded with Transforming Growth
Factor β (TGF-β) and All-Trans Retinoic Acid (ATRA), both well-known stimulators of T
regulatory cell (Treg) differentiation and stabilization. Male C57BL/6 mice were treated
with multiple low doses of streptozotocin for T1D induction, and with vehicle, empty MPs,
or ATRA- and TGF-β-loaded MPs for 10 days (every other day). Both T1D incidence and
immune cell infiltration into the pancreatic islets was lower in ATRA/TGF-β-treated mice.
In Peyer’s patches (PP), ATRA/TGF-β up-regulated tolerogenic dendritic cells (tolDC).
Additionally, IL-1β e xpression was r educed i n P P, a s w as t he r atio o f i NOS/Arginase
expression, reflecting a less inflammatory environment. This was accompanied by a
reduced proportion of Th1 and Th17 cells and up-regulation of Treg. IL-17 expression
within CD4+ T cells from PP was also lower, and was accompanied by down-regulation in
RORγt expression (key transcription factor of IL-17). The situation in the pancreatic
lymph nodes (PLN) was similar to PP regarding the down-regulation of Th1 cells.
Additionally, in response to ATRA/TGF-β treatment, the proliferation of T effector cells
was reduced in PLN, while Treg proliferated more, and several crucial markers of Treg
suppressive activity were increased. In conclusion, ATRA and TGF-β released from MPs
successfully ameliorated T1D by potentiating tolDC and Treg responses and inhibition of
Th1 cell differentiation in the draining lymph nodes, thus blocking the entrance of immune
cells into the pancreatic islets and protecting β-cells from further destruction.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.",
title = "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles",
pages = "113",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5778"
}
Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.
Belgrade: Faculty of Chemistry., 113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778
Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles. in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia.. 2019;:113.
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .
Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Suppresion of type 1 diabetes in mice by oral treatment with ATRA- and TGF-β-loaded microparticles" in The 9th Conference of the Serbian Biochemical Society: Diversity in Biochemistry; 2019 Nov 14-16; Belgrade, Serbia. (2019):113,
https://hdl.handle.net/21.15107/rcub_ibiss_5778 .

Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice

Koprivica, Ivan; Mićanović, Dragica; Saksida, Tamara; Cavalli, Eugenio; Auci, Dominick; Despotović, Sanja; Pejnović, Nada; Stošić-Grujičić, Stanislava; Nicoletti, Ferdinando; Stojanović, Ivana D.

(2019)

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Despotović, Sanja
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014299919306739?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3486
AB  - Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.
T2  - European Journal of Pharmacology
T1  - Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice
VL  - 864
DO  - 10.1016/j.ejphar.2019.172721
SP  - 172721
ER  - 
@article{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Despotović, Sanja and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Type 1 diabetes (T1D) is a multifactorial autoimmune disease that develops as a consequence of macrophage- and T cell-dependent pancreatic β-cell death. Multiple approaches for induction of anti-inflammatory/regulatory mechanisms that would attenuate T1D have been utilized, with little or no beneficial effects. To achieve prolonged stimulation of regulatory immune cells, we orally introduced microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and transforming growth factor-β (TGF-β) to C57BL/6 mice treated with multiple low doses of streptozotocin (MLDS) for T1D induction. Disease incidence was significantly lower in ATRA/TGF-β MPs-treated mice, as was the degree of immune cell infiltration into the pancreatic islets. In Peyer's patches (PP), ATRA/TGF-β MPs up-regulated tolerogenic dendritic cells (tolDCs) (CD11c+CD11b-CD103+), while the proportion of mature dendritic cells was not altered. This was accompanied by reduced Th1 and Th17 proportions and up-regulation of regulatory T cells (Tregs - CD4+CD25highFoxP3+). The immune cell composition in the pancreatic lymph nodes was similar to PP. Further, the proportion of effector Tbet+CD25med cells was decreased, while the proportion of Tbet+ Treg cells that specifically inhibit Th1 response was increased. Moreover, ATRA/TGF-β MPs treatment resulted in increased Treg proliferation and frequency of CTLA-4+PD1+ and CD39+IL-10+ Tregs, suggestive of their higher suppressive capacity. Reduced pancreatic infiltration may have been a consequence of lower cell capacity for matrix degradation. In conclusion, oral application of ATRA/TGF-β MPs ameliorated T1D through potentiation of tolDCs and Tregs, inhibition of Th1 response and prevention of the immune cell entrance into the islets.",
journal = "European Journal of Pharmacology",
title = "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice",
volume = "864",
doi = "10.1016/j.ejphar.2019.172721",
pages = "172721"
}
Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Despotović, S., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology, 864, 172721.
https://doi.org/10.1016/j.ejphar.2019.172721
Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Despotović S, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice. in European Journal of Pharmacology. 2019;864:172721.
doi:10.1016/j.ejphar.2019.172721 .
Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Despotović, Sanja, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Orally delivered all-trans-retinoic acid- and transforming growth factor-β-loaded microparticles ameliorate type 1 diabetes in mice" in European Journal of Pharmacology, 864 (2019):172721,
https://doi.org/10.1016/j.ejphar.2019.172721 . .
17
11
17

Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development

Koprivica, Ivan; Mićanović, Dragica; Saksida, Tamara; Cavalli, Eugenio; Auci, Dominick; Pejnović, Nada; Stošić-Grujičić, Stanislava; Nicoletti, Ferdinando; Stojanović, Ivana D.

(New York: Springer Nature, 2019)

TY  - CONF
AU  - Koprivica, Ivan
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Cavalli, Eugenio
AU  - Auci, Dominick
AU  - Pejnović, Nada
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Stojanović, Ivana D.
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5765
AB  - Background and aims: Type 1 diabetes (T1D) is a multifactorial autoimmune
disease that develops as a consequence of macrophage and T celldependent
pancreatic β cell death. Multiple approaches have been attempted
to induce anti-inflammatory/regulatory immune mechanisms that will attenuate
disease progression, with little or no beneficial effects. To achieve
prolonged stimulation of regulatory immune cells, our aim was to introduce
microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and
transforming growth factor β (TGF-β). Both molecules are well-known synergistic
stimulators of T regulatory cell (Treg) differentiation and stabilization.
Materials and methods: Male C57BL/6 mice were treated with multiple
low doses of streptozotocin (MLDS) for 5 consecutive days to induce
T1D, and with empty MPs or ATRA and TGF-β-loaded MPs (0.1% and
0.03% w/w, respectively) for 10 days (every other day, starting from the
first streptozotocin injection). Blood glucose was monitored on a weekly
basis and ex vivo analyses of immune cells (flow cytometry, qPCR, immunoblot)
were performed and pancreas histology was evaluated 14 days
from the beginning of the T1D induction. ANOVA t test was used for
statistical analysis and significant change was considered at p<0.05.
Results: T1D incidence was significantly lower inATRA/TGF-β MP-treated
mice, as was the degree of immune cell infiltration into the pancreatic islets. In
Peyer’s patches (PP), ATRA/TGF-β MPs up-regulated the tolerogenic population
of dendritic cells (DCs) (CD11c+CD11b-CD103+), while not altering
the proportion of mature DCs (CD11c+CD11b+). Additionally, both IL-1β
expression and production were reduced in PP, as was the ratio of
iNOS/Arginase mRNA expression, reflecting a less inflammatory environment.
This was accompanied by a reduction of the proportion of Th1
(CD4+IFN-γ+) and Th17 (CD4+IL-17+) cells and up-regulation of Treg
(CD4+CD25highFoxP3+). Lower IL-17 expression within CD4+ cells from
PP was in accordance with the observed down-regulation of RORγt
mRNA expression (key transcription factor of IL-17). The situation in the
pancreatic lymph nodes (PLN) was similar to PP regarding the downregulation
of inflammatory Th1 cells. Also, the proportion of
Tbet+CD25med cells (T effector cells) was lower, while the proportion of
Treg expressing T-bet was increased in PLN, suggesting that these cells specifically
mediate the inhibition of Th1 response. Additionally, in response to
ATRA/TGF-β MP treatment, the proliferation (Ki67+) of T effector cells was
reduced in PLN while Treg proliferated more. Furthermore, ATRA/TGF-β
MP treatment favored the presence of CTLA-4+PD1+ and CD39+IL-10+
populations of Treg and thus increased their suppressive activities.
Conclusion: ATRA and TGF-β released from MPs successfully ameliorated
T1D through the potentiation of tolDC and Treg response and inhibition
of Th1 cell differentiation in the draining lymph nodes, thereby
blocking the entrance of immune cells into the pancreatic islets and
protecting β cells from further destruction.
PB  - New York: Springer Nature
C3  - 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain
T1  - Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development
DO  - 10.1007/s00125-019-4946-6
SP  - S202
ER  - 
@conference{
author = "Koprivica, Ivan and Mićanović, Dragica and Saksida, Tamara and Cavalli, Eugenio and Auci, Dominick and Pejnović, Nada and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Stojanović, Ivana D.",
year = "2019",
abstract = "Background and aims: Type 1 diabetes (T1D) is a multifactorial autoimmune
disease that develops as a consequence of macrophage and T celldependent
pancreatic β cell death. Multiple approaches have been attempted
to induce anti-inflammatory/regulatory immune mechanisms that will attenuate
disease progression, with little or no beneficial effects. To achieve
prolonged stimulation of regulatory immune cells, our aim was to introduce
microparticles (MPs) loaded with all-trans retinoic acid (ATRA) and
transforming growth factor β (TGF-β). Both molecules are well-known synergistic
stimulators of T regulatory cell (Treg) differentiation and stabilization.
Materials and methods: Male C57BL/6 mice were treated with multiple
low doses of streptozotocin (MLDS) for 5 consecutive days to induce
T1D, and with empty MPs or ATRA and TGF-β-loaded MPs (0.1% and
0.03% w/w, respectively) for 10 days (every other day, starting from the
first streptozotocin injection). Blood glucose was monitored on a weekly
basis and ex vivo analyses of immune cells (flow cytometry, qPCR, immunoblot)
were performed and pancreas histology was evaluated 14 days
from the beginning of the T1D induction. ANOVA t test was used for
statistical analysis and significant change was considered at p<0.05.
Results: T1D incidence was significantly lower inATRA/TGF-β MP-treated
mice, as was the degree of immune cell infiltration into the pancreatic islets. In
Peyer’s patches (PP), ATRA/TGF-β MPs up-regulated the tolerogenic population
of dendritic cells (DCs) (CD11c+CD11b-CD103+), while not altering
the proportion of mature DCs (CD11c+CD11b+). Additionally, both IL-1β
expression and production were reduced in PP, as was the ratio of
iNOS/Arginase mRNA expression, reflecting a less inflammatory environment.
This was accompanied by a reduction of the proportion of Th1
(CD4+IFN-γ+) and Th17 (CD4+IL-17+) cells and up-regulation of Treg
(CD4+CD25highFoxP3+). Lower IL-17 expression within CD4+ cells from
PP was in accordance with the observed down-regulation of RORγt
mRNA expression (key transcription factor of IL-17). The situation in the
pancreatic lymph nodes (PLN) was similar to PP regarding the downregulation
of inflammatory Th1 cells. Also, the proportion of
Tbet+CD25med cells (T effector cells) was lower, while the proportion of
Treg expressing T-bet was increased in PLN, suggesting that these cells specifically
mediate the inhibition of Th1 response. Additionally, in response to
ATRA/TGF-β MP treatment, the proliferation (Ki67+) of T effector cells was
reduced in PLN while Treg proliferated more. Furthermore, ATRA/TGF-β
MP treatment favored the presence of CTLA-4+PD1+ and CD39+IL-10+
populations of Treg and thus increased their suppressive activities.
Conclusion: ATRA and TGF-β released from MPs successfully ameliorated
T1D through the potentiation of tolDC and Treg response and inhibition
of Th1 cell differentiation in the draining lymph nodes, thereby
blocking the entrance of immune cells into the pancreatic islets and
protecting β cells from further destruction.",
publisher = "New York: Springer Nature",
journal = "55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain",
title = "Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development",
doi = "10.1007/s00125-019-4946-6",
pages = "S202"
}
Koprivica, I., Mićanović, D., Saksida, T., Cavalli, E., Auci, D., Pejnović, N., Stošić-Grujičić, S., Nicoletti, F.,& Stojanović, I. D.. (2019). Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development. in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain
New York: Springer Nature., S202.
https://doi.org/10.1007/s00125-019-4946-6
Koprivica I, Mićanović D, Saksida T, Cavalli E, Auci D, Pejnović N, Stošić-Grujičić S, Nicoletti F, Stojanović ID. Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development. in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain. 2019;:S202.
doi:10.1007/s00125-019-4946-6 .
Koprivica, Ivan, Mićanović, Dragica, Saksida, Tamara, Cavalli, Eugenio, Auci, Dominick, Pejnović, Nada, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Stojanović, Ivana D., "Orally delivered microparticles loaded with all-trans retinoic acid and transforming growth factor β rescue mice from type 1 diabetes development" in 55th EASD Annual Meeting of the European Association for the Study of Diabetes; 2019 Sep 16-20; Barcelona, Spain (2019):S202,
https://doi.org/10.1007/s00125-019-4946-6 . .
4
18