Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
Аутори
Jonić, NatalijaChatzigiannis, Christos M.
Koprivica, Ivan
Marinho, Sérgio
Moura-Alves, Pedro
Pavić, Aleksandar
Otašević, Vesna
Pejnović, Nada
Tzakos, Andreas
Stojanović, Ivana
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 reg- ulatory 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 mod- ulating 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 im- munosuppressive Treg population.
Кључне речи:
AhR / immunomodulation / gut immunity / Treg / CYP1A1Извор:
CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia, 2023, 38-38Издавач:
- Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
Колекције
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Jonić, Natalija AU - Chatzigiannis, Christos M. AU - Koprivica, Ivan AU - Marinho, Sérgio AU - Moura-Alves, Pedro AU - Pavić, Aleksandar AU - Otašević, Vesna AU - Pejnović, Nada AU - Tzakos, Andreas AU - Stojanović, Ivana PY - 2023 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2112 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 reg- ulatory 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 mod- ulating 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 im- munosuppressive Treg population. PB - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade C3 - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia T1 - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut EP - 38 SP - 38 UR - https://hdl.handle.net/21.15107/rcub_imagine_2112 ER -
@conference{ author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana", 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 reg- ulatory 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 mod- ulating 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 im- munosuppressive Treg population.", publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade", journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia", title = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut", pages = "38-38", url = "https://hdl.handle.net/21.15107/rcub_imagine_2112" }
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 38-38. https://hdl.handle.net/21.15107/rcub_imagine_2112
Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović I. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:38-38. https://hdl.handle.net/21.15107/rcub_imagine_2112 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana, "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):38-38, https://hdl.handle.net/21.15107/rcub_imagine_2112 .