DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells

摘要: Summary Inflammatory bowel disease (IBD) is a complex autoimmune disorder recently shown to be associated with SUMOylation, post-translational modification mechanism. Here, we have identified link between epithelial deSUMOylases and inflammation in IBD. DeSUMOylase SENP7 was seen upregulated specifically intestinal cells both human IBD mouse model. In steady state, but not IBD, expression negatively regulated by direct interaction ubiquitination SIAH2. Upregulated inflamed tissue displayed distinct interactome. These changes led an expansion of localized proinflammatory γδ T cells. Furthermore, in vivo knockdown or depletion T cells abrogated dextran sulfate sodium (DSS)-induced gut inflammation. Strong statistical correlations high clinical indices were observed patients. Overall, our data reveal that necessary sufficient for controlling inflammation, thus highlighting its importance as potential drug target.