TY  - CONF
AU  - Jonić, Natalija
AU  - Koprivica, Ivan
AU  - Chatzigiannis, Christos
AU  - Tsiailanis, Antonis
AU  - Kyrkou, Stavroula
AU  - Tzakos, Eleftherios Paraskevas
AU  - Pavić, Aleksandar
AU  - Dimitrijević, Mirjana
AU  - Jovanović, Anđelina
AU  - Jovanović, Milan B.
AU  - Marinho, Sergio
AU  - Castro-Almeida, Ines
AU  - Otašević, Vesna
AU  - Moura-Alves, Pedro
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/7017
AB  - Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by an imbalance between pathogenic CD4+ and
CD8+ lymphocytes on one side and regulatory T cells (Treg) on the other. Activating Treg and/or tolerogenic dendritic
cells (tolDC) through various methods has shown benefits in animal models of T1D. Both cell types express high levels
of the aryl hydrocarbon receptor (AHR), and AHR activation is typically associated with enhanced tolDC and Treg
functionality. In this study, the novel fluorescent indole-containing compound AGT-5 was investigated for its potential
to act as an AHR ligand and modulate immune cells both in vitro and in vivo. Through in silico docking analysis, AGT-
5 demonstrated the ability to bind AHR, and its agonistic effects were confirmed using the reporter Caco-2 cell line.
Additionally, due to its fluorescent properties, AGT-5 was visualized in macrophages in vitro and in the small intestine
lamina propria ex vivo after oral administration using confocal microscopy. AGT-5 exhibited no toxicity towards murine
macrophages and human tonsillar cells. Moreover, tests on zebrafish embryos revealed no nephrotoxicity, hepatotoxicity,
or cardiotoxicity. Utilizing an ADME virtual platform it was confirmed that AGT-5 possesses drug-like characteristics.
Subsequently, AGT-5 was orally administered to C57BL/6 mice that had received low doses of streptozotocin to induce
T1D. Treatment with AGT-5 commencing from the first day of T1D induction and lasting for 20 days effectively
prevented immune cell infiltration into the pancreas, preserved insulin production, and halted the progression of T1D.
AGT-5 achieved this by promoting tolDC and Treg activity along the gut-pancreatic lymph node-pancreas axis.
Mechanistically, AGT-5 upregulated indoleamine 2,3-dioxygenase 1 in tolDC and enhanced ATP-degrading enzyme
expression on Treg, thereby promoting immunosuppressive action. The positive outcomes seen in T1D animals suggest
that AGT-5 holds promise for a potential treatment for inflammatory conditions that can benefit from stimulation of the
regulatory arm of the immune response.
PB  - John Wiley and Sons
C3  - 7th European Congress of Immunology: ECI 2024; 2024 Sep 1-4; Dublin, Ireland
T1  - A novel aryl hydrocarbon receptor ligand inhibits the development of Type 1 diabetes by enhancing the function of tolerogenic dendritic cells and regulatory T cells
IS  - 54
DO  - 10.1002/eji.202470200
SP  - 372
EP  - 373
ER  - 

@conference{
author = "Jonić, Natalija and Koprivica, Ivan and Chatzigiannis, Christos and Tsiailanis, Antonis and Kyrkou, Stavroula and Tzakos, Eleftherios Paraskevas and Pavić, Aleksandar and Dimitrijević, Mirjana and Jovanović, Anđelina and Jovanović, Milan B. and Marinho, Sergio and Castro-Almeida, Ines and Otašević, Vesna and Moura-Alves, Pedro and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2024",
abstract = "Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by an imbalance between pathogenic CD4+ and
CD8+ lymphocytes on one side and regulatory T cells (Treg) on the other. Activating Treg and/or tolerogenic dendritic
cells (tolDC) through various methods has shown benefits in animal models of T1D. Both cell types express high levels
of the aryl hydrocarbon receptor (AHR), and AHR activation is typically associated with enhanced tolDC and Treg
functionality. In this study, the novel fluorescent indole-containing compound AGT-5 was investigated for its potential
to act as an AHR ligand and modulate immune cells both in vitro and in vivo. Through in silico docking analysis, AGT-
5 demonstrated the ability to bind AHR, and its agonistic effects were confirmed using the reporter Caco-2 cell line.
Additionally, due to its fluorescent properties, AGT-5 was visualized in macrophages in vitro and in the small intestine
lamina propria ex vivo after oral administration using confocal microscopy. AGT-5 exhibited no toxicity towards murine
macrophages and human tonsillar cells. Moreover, tests on zebrafish embryos revealed no nephrotoxicity, hepatotoxicity,
or cardiotoxicity. Utilizing an ADME virtual platform it was confirmed that AGT-5 possesses drug-like characteristics.
Subsequently, AGT-5 was orally administered to C57BL/6 mice that had received low doses of streptozotocin to induce
T1D. Treatment with AGT-5 commencing from the first day of T1D induction and lasting for 20 days effectively
prevented immune cell infiltration into the pancreas, preserved insulin production, and halted the progression of T1D.
AGT-5 achieved this by promoting tolDC and Treg activity along the gut-pancreatic lymph node-pancreas axis.
Mechanistically, AGT-5 upregulated indoleamine 2,3-dioxygenase 1 in tolDC and enhanced ATP-degrading enzyme
expression on Treg, thereby promoting immunosuppressive action. The positive outcomes seen in T1D animals suggest
that AGT-5 holds promise for a potential treatment for inflammatory conditions that can benefit from stimulation of the
regulatory arm of the immune response.",
publisher = "John Wiley and Sons",
journal = "7th European Congress of Immunology: ECI 2024; 2024 Sep 1-4; Dublin, Ireland",
title = "A novel aryl hydrocarbon receptor ligand inhibits the development of Type 1 diabetes by enhancing the function of tolerogenic dendritic cells and regulatory T cells",
number = "54",
doi = "10.1002/eji.202470200",
pages = "372-373"
}

Jonić, N., Koprivica, I., Chatzigiannis, C., Tsiailanis, A., Kyrkou, S., Tzakos, E. P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., Marinho, S., Castro-Almeida, I., Otašević, V., Moura-Alves, P., Tzakos, A.,& Stojanović, I. D.. (2024). A novel aryl hydrocarbon receptor ligand inhibits the development of Type 1 diabetes by enhancing the function of tolerogenic dendritic cells and regulatory T cells. in 7th European Congress of Immunology: ECI 2024; 2024 Sep 1-4; Dublin, Ireland
John Wiley and Sons.(54), 372-373.
https://doi.org/10.1002/eji.202470200

Jonić N, Koprivica I, Chatzigiannis C, Tsiailanis A, Kyrkou S, Tzakos EP, Pavić A, Dimitrijević M, Jovanović A, Jovanović MB, Marinho S, Castro-Almeida I, Otašević V, Moura-Alves P, Tzakos A, Stojanović ID. A novel aryl hydrocarbon receptor ligand inhibits the development of Type 1 diabetes by enhancing the function of tolerogenic dendritic cells and regulatory T cells. in 7th European Congress of Immunology: ECI 2024; 2024 Sep 1-4; Dublin, Ireland. 2024;(54):372-373.
doi:10.1002/eji.202470200 .

Jonić, Natalija, Koprivica, Ivan, Chatzigiannis, Christos, Tsiailanis, Antonis, Kyrkou, Stavroula, Tzakos, Eleftherios Paraskevas, Pavić, Aleksandar, Dimitrijević, Mirjana, Jovanović, Anđelina, Jovanović, Milan B., Marinho, Sergio, Castro-Almeida, Ines, Otašević, Vesna, Moura-Alves, Pedro, Tzakos, Andreas, Stojanović, Ivana D., "A novel aryl hydrocarbon receptor ligand inhibits the development of Type 1 diabetes by enhancing the function of tolerogenic dendritic cells and regulatory T cells" in 7th European Congress of Immunology: ECI 2024; 2024 Sep 1-4; Dublin, Ireland, no. 54 (2024):372-373,
https://doi.org/10.1002/eji.202470200 . .

TY  - JOUR
AU  - Jonić, Natalija
AU  - Koprivica, Ivan
AU  - Kyrkou, Stavroula G
AU  - Bistas, Vasileios-Panagiotis
AU  - Chatzigiannis, Christos
AU  - Radulović, Nataša
AU  - Pilipović, Ivan
AU  - Jovanović, Anđelina
AU  - Jovanović, Milan B.
AU  - Dimitrijević, Mirjana
AU  - Tzakos, Andreas G
AU  - Stojanović, Ivana D.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6998
AB  - Type 1 diabetes (T1D) is an autoimmune disease with a strong chronic
inflammatory component. One possible strategy for the treatment of T1D is to
stimulate the regulatory arm of the immune response, i.e. to promote the
function of tolerogenic dendritic cells (tolDC) and regulatory T cells (Treg).
Since both cell types have been shown to be responsive to the aryl
hydrocarbon receptor (AHR) activation, we used a recently characterized
member of a new class of fluorescent AHR ligands, AGT-5, to modulate
streptozotocin-induced T1D in C57BL/6 mice. Prophylactic oral administration
of AGT-5 reduced hyperglycemia and insulitis in these mice. Phenotypic and
functional analysis of cells in the pancreatic infiltrates of AGT-5-treated mice (at
the early phase of T1D) revealed a predominantly anti-inflammatory
environment, as evidenced by the upregulation of tolDC and Treg frequency,
while CD8+ cell, Th1 and Th17 cells were significantly reduced. Similarly, AGT-5
enhanced the proportion of Treg and tolDC in small intestine lamina propria and
suppressed the activation status of antigen-presenting cells through downregulation of co-stimulatory molecules CD40, CD80 and CD86. The
expression levels of Cyp1a1, controlled by the AHR, were increased in CD4+,
CD8+ and Treg, confirming the AHR-mediated effect of AGT-5 in these cells.
Finally, AGT-5 stimulated the function of regulatory cells in the pancreatic islets
and lamina propria by upregulating indoleamine 2,3-dioxigenase 1 (IDO1) in
tolDC. These findings were supported by the abrogation of AGT-5-mediated in
vitro effects on DC in the presence of IDO1 inhibitor. AGT-5 also increased the
expression of CD39 or CD73 ATP-degrading ectoenzymes by Treg. The increase
in Treg is further supported by the upregulated frequency of IL-2-producing type
3 innate lymphoid cells (ILC3) in the lamina propria. Anti-inflammatory effects of
AGT-5 were also validated on human tonsil cells, where in vitro exposure to AGT-
5 increased the proportion of immunosuppressive dendritic cells and ILC3. These results suggest that AGT-5, by stimulating AHR, may promote a general
immunosuppressive environment in the pancreas and small intestine lamina
propria at the early phase of disease, and thereby inhibit the severity of T1D
in mice.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Immunology
T1  - Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease
VL  - 15
DO  - 10.3389/fimmu.2024.1454156
SP  - 1454156
ER  - 

@article{
author = "Jonić, Natalija and Koprivica, Ivan and Kyrkou, Stavroula G and Bistas, Vasileios-Panagiotis and Chatzigiannis, Christos and Radulović, Nataša and Pilipović, Ivan and Jovanović, Anđelina and Jovanović, Milan B. and Dimitrijević, Mirjana and Tzakos, Andreas G and Stojanović, Ivana D.",
year = "2024",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease with a strong chronic
inflammatory component. One possible strategy for the treatment of T1D is to
stimulate the regulatory arm of the immune response, i.e. to promote the
function of tolerogenic dendritic cells (tolDC) and regulatory T cells (Treg).
Since both cell types have been shown to be responsive to the aryl
hydrocarbon receptor (AHR) activation, we used a recently characterized
member of a new class of fluorescent AHR ligands, AGT-5, to modulate
streptozotocin-induced T1D in C57BL/6 mice. Prophylactic oral administration
of AGT-5 reduced hyperglycemia and insulitis in these mice. Phenotypic and
functional analysis of cells in the pancreatic infiltrates of AGT-5-treated mice (at
the early phase of T1D) revealed a predominantly anti-inflammatory
environment, as evidenced by the upregulation of tolDC and Treg frequency,
while CD8+ cell, Th1 and Th17 cells were significantly reduced. Similarly, AGT-5
enhanced the proportion of Treg and tolDC in small intestine lamina propria and
suppressed the activation status of antigen-presenting cells through downregulation of co-stimulatory molecules CD40, CD80 and CD86. The
expression levels of Cyp1a1, controlled by the AHR, were increased in CD4+,
CD8+ and Treg, confirming the AHR-mediated effect of AGT-5 in these cells.
Finally, AGT-5 stimulated the function of regulatory cells in the pancreatic islets
and lamina propria by upregulating indoleamine 2,3-dioxigenase 1 (IDO1) in
tolDC. These findings were supported by the abrogation of AGT-5-mediated in
vitro effects on DC in the presence of IDO1 inhibitor. AGT-5 also increased the
expression of CD39 or CD73 ATP-degrading ectoenzymes by Treg. The increase
in Treg is further supported by the upregulated frequency of IL-2-producing type
3 innate lymphoid cells (ILC3) in the lamina propria. Anti-inflammatory effects of
AGT-5 were also validated on human tonsil cells, where in vitro exposure to AGT-
5 increased the proportion of immunosuppressive dendritic cells and ILC3. These results suggest that AGT-5, by stimulating AHR, may promote a general
immunosuppressive environment in the pancreas and small intestine lamina
propria at the early phase of disease, and thereby inhibit the severity of T1D
in mice.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Immunology",
title = "Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease",
volume = "15",
doi = "10.3389/fimmu.2024.1454156",
pages = "1454156"
}

Jonić, N., Koprivica, I., Kyrkou, S. G., Bistas, V., Chatzigiannis, C., Radulović, N., Pilipović, I., Jovanović, A., Jovanović, M. B., Dimitrijević, M., Tzakos, A. G.,& Stojanović, I. D.. (2024). Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease. in Frontiers in Immunology
Lausanne: Frontiers Media SA., 15, 1454156.
https://doi.org/10.3389/fimmu.2024.1454156

Jonić N, Koprivica I, Kyrkou SG, Bistas V, Chatzigiannis C, Radulović N, Pilipović I, Jovanović A, Jovanović MB, Dimitrijević M, Tzakos AG, Stojanović ID. Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease. in Frontiers in Immunology. 2024;15:1454156.
doi:10.3389/fimmu.2024.1454156 .

Jonić, Natalija, Koprivica, Ivan, Kyrkou, Stavroula G, Bistas, Vasileios-Panagiotis, Chatzigiannis, Christos, Radulović, Nataša, Pilipović, Ivan, Jovanović, Anđelina, Jovanović, Milan B., Dimitrijević, Mirjana, Tzakos, Andreas G, Stojanović, Ivana D., "Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease" in Frontiers in Immunology, 15 (2024):1454156,
https://doi.org/10.3389/fimmu.2024.1454156 . .

TY  - JOUR
AU  - Jonić, Natalija
AU  - Koprivica, Ivan
AU  - Chatzigiannis, Christos M.
AU  - Tsiailanis, Antonis D.
AU  - Kyrkou, Stavroula G
AU  - Tzakos, Eleftherios Paraskevas
AU  - Pavić, Aleksandar
AU  - Dimitrijević, Mirjana
AU  - Jovanović, Andjelina
AU  - Jovanović, Milan B.
AU  - Marinho, Sergio
AU  - Castro-Almeida, Ines
AU  - Otašević, Vesna
AU  - Moura-Alves, Pedro
AU  - Tzakos, Andreas G
AU  - Stojanović, Ivana D.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6870
AB  - Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects.
In this study, we designed, synthesized and evaluated three indole-containing potential AHR
ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to
emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in
silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs
were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their
immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant
anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory
regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5
actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation,
cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator
of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also
observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish
embryos and was therefore considered safe for animal studies. Following oral administration to
C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1
cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized
both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the
small intestine). These findings make AGT-5 a promising candidate for further exploration in the
treatment of inflammatory and autoimmune diseases.
PB  - Basel: MDPI
T2  - Molecules
T1  - Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells
IS  - 13
VL  - 29
DO  - 10.3390/molecules29132988
SP  - 2988
ER  - 

@article{
author = "Jonić, Natalija and Koprivica, Ivan and Chatzigiannis, Christos M. and Tsiailanis, Antonis D. and Kyrkou, Stavroula G and Tzakos, Eleftherios Paraskevas and Pavić, Aleksandar and Dimitrijević, Mirjana and Jovanović, Andjelina and Jovanović, Milan B. and Marinho, Sergio and Castro-Almeida, Ines and Otašević, Vesna and Moura-Alves, Pedro and Tzakos, Andreas G and Stojanović, Ivana D.",
year = "2024",
abstract = "Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects.
In this study, we designed, synthesized and evaluated three indole-containing potential AHR
ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to
emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in
silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs
were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their
immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant
anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory
regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5
actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation,
cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator
of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also
observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish
embryos and was therefore considered safe for animal studies. Following oral administration to
C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1
cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized
both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the
small intestine). These findings make AGT-5 a promising candidate for further exploration in the
treatment of inflammatory and autoimmune diseases.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells",
number = "13",
volume = "29",
doi = "10.3390/molecules29132988",
pages = "2988"
}

Jonić, N., Koprivica, I., Chatzigiannis, C. M., Tsiailanis, A. D., Kyrkou, S. G., Tzakos, E. P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., Marinho, S., Castro-Almeida, I., Otašević, V., Moura-Alves, P., Tzakos, A. G.,& Stojanović, I. D.. (2024). Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells. in Molecules
Basel: MDPI., 29(13), 2988.
https://doi.org/10.3390/molecules29132988

Jonić N, Koprivica I, Chatzigiannis CM, Tsiailanis AD, Kyrkou SG, Tzakos EP, Pavić A, Dimitrijević M, Jovanović A, Jovanović MB, Marinho S, Castro-Almeida I, Otašević V, Moura-Alves P, Tzakos AG, Stojanović ID. Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells. in Molecules. 2024;29(13):2988.
doi:10.3390/molecules29132988 .

Jonić, Natalija, Koprivica, Ivan, Chatzigiannis, Christos M., Tsiailanis, Antonis D., Kyrkou, Stavroula G, Tzakos, Eleftherios Paraskevas, Pavić, Aleksandar, Dimitrijević, Mirjana, Jovanović, Andjelina, Jovanović, Milan B., Marinho, Sergio, Castro-Almeida, Ines, Otašević, Vesna, Moura-Alves, Pedro, Tzakos, Andreas G, Stojanović, Ivana D., "Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells" in Molecules, 29, no. 13 (2024):2988,
https://doi.org/10.3390/molecules29132988 . .

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 .