TRAF5 regulates intestinal mucosal Th1/Th17 cell immune responses via Runx1 in colitis mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor‐associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS‐induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5−/− CD4+CD45RBhigh T cells and WT CD4+CD45RBhigh T cells were transferred to Rag2−/− mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model. Adeno‐associated virus (AAV)‐mediated gene knockout technique was used to knock out runt‐associated transcription factor 1 (Runx1) expression in vivo. Specific cytokines of Th1 and Th17 cells were detected by quantitative RT‐PCR, immunohistochemistry, ELISA, and flow cytometry. In T‐cell transfer colitis mice, the Rag2−/− mice reconstituted with TRAF5−/− CD4+CD45RBhigh T cells showed more severe intestinal inflammation than the WT control group, which was characterised by increased expression of INF‐γ, TNF‐α, IL‐17a. Furthermore, we found that the INF‐γ+CD4+, IL17a+CD4+, and INF‐γ+ IL17a+CD4+ T cells in the intestinal mucosa of Rag2−/− mice reconstituted with TRAF5−/− CD4+CD45RBhigh T cells were significantly higher than those of the WT control group by flow cytometry. Mechanistically, knockout Runx1 inhibited the differentiation of TRAF5−/− CD4+ T cells into Th1 and Th17 cells in the intestinal mucosa of T‐cell transfer colitis mice. TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis. Thus targeting TRAF5 in CD4+ T cells may be a novel treatment for IBD. [ABSTRACT FROM AUTHOR]