biostudies-literatureSuhail ARegional Centre for BiotechnologyDBT/Wellcome Trust India AllianceWellcome Trust/DBTWellcome Trust3522-3538.e7https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617169biostudies-literatureUnknown29(11)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 coCell reportsDeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells.PMC7617169IA/I/11/2500284Gaur PMujagond PAhuja VSuhail ASingh MAwasthi ASrikanth CVRizvi ZAAli SAfalseDeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells.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 co2019-01-01T00:00:00Z2019 Dec2026-06-01T16:14:40.275Z2025-04-03T23:32:42.897ZS-EPMC76171693182583310.1016/j.celrep.2019.11.028