Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
2023
Authors:
Jonić, NatalijaChatzigiannis, Christos M.
Koprivica, Ivan
Marinho, Sergio
Moura-Alves, Pedro
Pavić, Aleksandar
Otašević, Vesna
Pejnović, Nada
Tzakos, Andreas
Stojanović, Ivana D.
Contributors
Dobrijević, ZoranaDocument Type:
Conference object (Published version)
,
© 2023 by the Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
Metadata
Show full item recordAbstract:
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.
Keywords:
AhR; immunomodulation; gut immunity; Treg; CYP1A1Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- Dobrijević Z, editor. 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 ; 2023. p. 38. (Trends in Molecular Biology; Special Issue).