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

ABSTRACT: Inflammatory bowel disease (IBD) is a complex autoimmune disorder recently shown to be associated with SUMOylation, a post-translational modification mechanism. Here, we have identified a link between epithelial deSUMOylases and inflammation in IBD. DeSUMOylase SENP7 was seen to be upregulated specifically in intestinal epithelial cells in both human IBD and a mouse model. In steady state, but not IBD, SENP7 expression was negatively regulated by a direct interaction and ubiquitination by SIAH2. Upregulated SENP7 in inflamed tissue displayed a distinct interactome. These changes led to an expansion of localized proinflammatory γδ T cells. Furthermore, in vivo knockdown of SENP7 or depletion of γδ T cells abrogated dextran sulfate sodium (DSS)-induced gut inflammation. Strong statistical co

SUBMITTER: Suhail A 

PROVIDER: S-EPMC7617169 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature