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

作者：Mengting Li, Caiqin Gan, Runan Zhang, Jiahui Wang, Youwei Wang, Weining Zhu, Lan Liu, Jian Shang, Qiu Zhao · 发表于：Immunology · 年份：2023 · DOI：10.1111/imm.13685 · 被引用次数：9 · 研究领域：NF-κB Signaling Pathways、Inflammatory Bowel Disease、Helicobacter pylori-related gastroenterology studies

Abstract 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 t...