Negative Regulation Of IL-17-mediated Signaling By The Aryl Hydrocarbon Receptor

IL-17(interleukin-17), mainly produced by Th17(T-helper17) cells, plays important functions in host defence against bacterial and fungal infections, as well as in the pathogenesis of various human autoimmune diseases. We identified the aryl hydrocarbon receptor as a negative regulator of IL-17-mediated signaling. AHR is a ligand-activated transcription factor that serves not only as a receptor for various environmental toxins but also plays an important function in the immune system, especially as the transcription factors can regulate Th17cell differentiation. At present, it is still unclear AHR is able to play a role in IL-17signaling pathway. This research showed that activation or overexpression of AHR inhibited IL-17induced production of chemokine CXCL2, CCL20and cytokines IL-6in Hela cells. Silencing of AHR promoted the chemokine CXCL2, CCL20and cytokines IL-6production in Hela cells. We did further experiment and discovered that activation of AHR inhibited IL-17induced phosphorylation of P38and silencing of AHR promotes P38phosphorylation in Hela cells. We confirmed that the P38inhibitor significantly reversed the promoting effect of IL-17-induced cytokines expression mediated by AHR silencing. We selected10cases of ulcerative colitis and10normal colon tissue sections for Immunohistochemistry analysis found AHR protein low expression in ulcerative colitis. These results demonstrated that AHR played an important function in inflammatory bowel disease. In vitro experiments showed that aryl hydrocarbon receptor could negative regulated IL-17-mediated signaling while the expression was negative correlation with ulcerative colitis. It showed that AHR could inhibit the occurrence and development of ulcerative colitis (UC) through the negative regulation of IL-17-mediated inflammatory effect.