Dataset Information

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):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Colon

SUBMITTER: CV srikanth

LAB HEAD: Dr C. V. Srikanth

PROVIDER: PXD016018 | Pride | 2025-05-06

REPOSITORIES: Pride

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

Suhail Aamir A Rizvi Zaigham Abbas ZA Mujagond Prabhakar P Ali Syed Azmal SA Gaur Preksha P Singh Mukesh M Ahuja Vineet V Awasthi Amit A Srikanth Chittur Venkateshwaran CV

Cell reports 20191201 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. ...[more]

PMID: 31825833

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