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 + CD45RB high T cells and WT CD4 + CD45RB high 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 + CD45RB high 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 + CD45RB high 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.