Ahr-Foxp3-RORγt axis controls gut homing of CD4⁺ T cells by regulating GPR15.

ABSTRACT: The orphan chemoattractant receptor GPR15 is important for homing T lymphocytes to the large intestine, thereby maintaining intestinal immune homeostasis. However, the molecular mechanisms underlying the regulation of GPR15 expression remain elusive. Here, we show a central role of the aryl hydrocarbon receptor (Ahr) in promoting GPR15 expression in both mice and human, thus gut homing of T lymphocytes. Mechanistically, Ahr directly binds to open chromatin regions of the Gpr15 locus to enhance its expression. Ahr transcriptional activity in directing GPR15 expression was modulated by two transcription factors, Foxp3 and RORγt, both of which are expressed preferentially by gut regulatory T cells (T_regs) in vivo. Specifically, Foxp3 interacted with Ahr and enhanced Ahr DNA

SUBMITTER: Xiong L 

PROVIDER: S-EPMC7371246 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature