| First Author | Suhail A | Year | 2019 |
| Journal | Cell Rep | Volume | 29 |
| Issue | 11 | Pages | 3522-3538.e7 |
| PubMed ID | 31825833 | Mgi Jnum | J:297790 |
| Mgi Id | MGI:6479268 | Doi | 10.1016/j.celrep.2019.11.028 |
| Citation | Suhail A, et al. (2019) DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells. Cell Rep 29(11):3522-3538.e7 |
| abstractText | 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 gammadelta T cells. Furthermore, in vivo knockdown of SENP7 or depletion of gammadelta T cells abrogated dextran sulfate sodium (DSS)-induced gut inflammation. Strong statistical correlations between upregulated SENP7 and high clinical disease indices were observed in IBD patients. Overall, our data reveal that epithelial SENP7 is necessary and sufficient for controlling gut inflammation, thus highlighting its importance as a potential drug target. |
