TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos
AU  - Tsiailanis, Antonis
AU  - Tzakos, Andreas G
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6474
AB  - Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6474
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Chatzigiannis, Christos and Tsiailanis, Antonis and Tzakos, Andreas G and Stojanović, Ivana D.",
year = "2023",
abstract = "Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6474"
}

Koprivica, I., Jonić, N., Chatzigiannis, C., Tsiailanis, A., Tzakos, A. G.,& Stojanović, I. D.. (2023). Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474

Koprivica I, Jonić N, Chatzigiannis C, Tsiailanis A, Tzakos AG, Stojanović ID. Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

Koprivica, Ivan, Jonić, Natalija, Chatzigiannis, Christos, Tsiailanis, Antonis, Tzakos, Andreas G, Stojanović, Ivana D., "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

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 .

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 .

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 .

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 . .

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 . .

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 .

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 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Mićanović, Dragica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
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/123456789/4877
AB  - Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model
DO  - 10.1002/eji.202170200
SP  - 399
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Papaemmanouil, Christina and Mićanović, Dragica and Stegnjaić, Goran and Jevtić, Bojan and Saksida, Tamara and Miljković, Đorđe and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model",
doi = "10.1002/eji.202170200",
pages = "399"
}

Koprivica, I., Jonić, N., Diamantis, D., Papaemmanouil, C., Mićanović, D., Stegnjaić, G., Jevtić, B., Saksida, T., Miljković, Đ., Tzakos, A.,& Stojanović, I. D.. (2021). Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 399.
https://doi.org/10.1002/eji.202170200

Koprivica I, Jonić N, Diamantis D, Papaemmanouil C, Mićanović D, Stegnjaić G, Jevtić B, Saksida T, Miljković Đ, Tzakos A, Stojanović ID. Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:399.
doi:10.1002/eji.202170200 .

Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Papaemmanouil, Christina, Mićanović, Dragica, Stegnjaić, Goran, Jevtić, Bojan, Saksida, Tamara, Miljković, Đorđe, Tzakos, Andreas, Stojanović, Ivana D., "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):399,
https://doi.org/10.1002/eji.202170200 . .