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Aryl hydrocarbon receptor engagement during redox alteration determines the fate of CD4 + T cells in C57BL/6 mice
Author(s) -
Mohammadi Hamidreza,
Daryabor Gholamreza,
Ghaffarian Bahraman Ali,
Keshavarzi Majid,
Kalantar Kurosh,
MohammadiBardbori Afshin
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22821
Subject(s) - aryl hydrocarbon receptor , chemistry , gclm , hmox1 , splenocyte , cell growth , glutathione , gclc , in vitro , downregulation and upregulation , biochemistry , transcription factor , gene , enzyme , heme , heme oxygenase
The preservation of the redox homeostasis is critical for cell survival and functionality. Redox imbalance is an essential inducer of several pathological states. CD4 + /helper T cells are highly dependent on the redox state of their surrounding milieu. The potential of the aryl hydrocarbon receptor (AhR) engagement in controlling CD4 + T‐cell fate during redox alteration is still challenging. C57BL/6 mice were treated with AhR agonist 6‐formylindolo[3,2‐b]carbazole (FICZ), AhR antagonist CH223191, an inhibitor of glutathione biosynthesis buthionine sulfoximine (BSO), and the antioxidant N ‐acetylcysteine (NAC) alone or in combination. Six days later, splenocytes were evaluated for the expression of the redox‐related genes and the possible changes in T‐cell subsets. FICZ like BSO significantly elevated the expression of HMOX1, GCLC, and GCLM genes but it failed to increase the expression of the Nrf2 gene. Moreover, FICZ + BSO increased while FICZ + CH223191 or NAC decreased the expression of these genes. FICZ also significantly increased Th1 cell numbers but decreased Tregs in a dose‐dependent manner. Furthermore, a high dose of FICZ + CH223191 + NAC significantly enhanced Th1, Th17, and Treg cells but its low dose in such a situation increased Th2 and Th17 while decreased Treg cells. AhR engagement during redox alteration can determine the fate of CD4 + T cells, so, AhR agonists or antagonists might be useful in assessing immune responses. However, these results need further verifications in vitro and in animal models of various diseases.