DeSUMOylase SENP7 mediated epithelial signaling triggers intestinal inflammation via expansion of Gamma-delta T cell

ABSTRACT: Inflammatory bowel disease (IBD) is a complex autoimmune disorder and recently shown to be associated with SUMOylation, a post-translational modification mechanism. Here we have identified a link between De-SUMOylases and tissue inflammation in IBD. SENP7, a deSUMOylase was seen to be explicitly upregulatedupregulated specifically in intestinal epithelial cells of animal model and human IBD patient samples. SENP7 expression was negatively regulated by a direct interaction and ubiquitination by SIAH2. This control was lost in inflamed cells, leading to SENP7 upregulation allowing access to a distinct SENP7 interactome revealed by complex mass-spectrometry. Furthermore, in vivo Knock-Down of SENP7 or pharmacological induction of SIAH2 abrogated DSS-induced gut inflammation. Explicitly, SENP7 upregulation led to an expansion of localized γδT cells triggering a proinflammatory environment. Strong statistical correlation between upregulated SENP7 and high clinical disease indices were observed in IBD patients. Overall our data reveal that epithelial SENP7 is necessary and sufficient in controlling gut inflammation, thus highlighting its importance as a potential drug target.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Colon

SUBMITTER: CV srikanth  

LAB HEAD: Dr. C. V. Srikanth

PROVIDER: PXD015994 | Pride | 2025-05-06

REPOSITORIES: Pride