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 .