Aryl hydrocarbon receptor activation modulates CD8αα(+)TCRαβ(+) IELs and suppression of colitis manifestations in mice.

BACKGROUND: This research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis.

METHODS: Colitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration. The mice were weighed and assessed, and colon tissues were measured. Intraepithelial lymphocytes (IELs) were isolated from the colon and examined by flow cytometry and quantitative real-time PCR.

RESULTS: FICZ ameliorated DSS-induced colitis, resulting in a reduced disease activity index and improvement in the histology and length of the colon. Colitis reduced the percentage and number of CD8αα(+)TCRαβ(+) IELs. FICZ prevented the reduction in the numbers of CD8αα(+)TCRαβ(+) IELs by upregulating the expression of the IL-15 receptor and the aryl hydrocarbon receptor (AhR), and attenuating the apoptotic rate of CD8αα(+)TCRαβ(+) IELs. Finally, IL-10 was increased and IFN-γ was decreased in CD8αα(+)TCRαβ(+) IELs by FICZ administration in DSS-induced colitis.

CONCLUSIONS: The results suggest that AhR activation ameliorated DSS-induced acute colitis, in a manner that is associated with the local expansion and functions of CD8αα(+)TCRαβ(+) IELs in acute colitis. The findings indicate that AhR-related ligands might be targeted as novel drug targets for IBD.