Suhail, Aamir and Rizvi, Zaigham Abbas and Mujagond, Prabhakar and Ali, Syed Azmal and Gaur, Preksha and Singh, Mukesh and Ahuja, Vineet and Awasthi, Amit and Srikanth, Chittur Venkateshwaran (2019) DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells. Cell Reports, 29 (11). 3522-3538.e7. ISSN 22111247

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Abstract

Cell ReportsArticleDeSUMOylase SENP7-Mediated EpithelialSignaling Triggers Intestinal Inflammationvia Expansion of Gamma-Delta T CellsAamir Suhail,1,2Zaigham Abbas Rizvi,3,6Prabhakar Mujagond,1,6Syed Azmal Ali,4Preksha Gaur,1Mukesh Singh,5Vineet Ahuja,5,*Amit Awasthi,2,*and Chittur Venkateshwaran Srikanth1,7,*1Regional Centre for Biotechnology, 3rdmilestone Gurgaon-Faridabad Expressway, Faridabad 121001, India2Kalinga Institute of Industrial Technology, Bhubaneshwar, 751016 Orissa, India3Translational Health Science and Technology Institute, 3rdMilestone Gurgaon-Faridabad expressway, Faridabad 121001, India4Animal Biotechnology Centre, National Dairy Research Institute, Karnal, Haryana 132001, India5All India Institute of Medical Sciences, Ansari Nagar East, New Delhi 110023, India6These authors contributed equally7Lead Contact*Correspondence:vins_ahuja@hotmail.com(V.A.),aawasthi@thsti.res.in(A.A.),cvsrikanth@rcb.res.in(C.V.S.)https://doi.org/10.1016/j.celrep.2019.11.028SUMMARYInflammatory bowel disease (IBD) is a complex auto-immune disorder recently shown to be associatedwith SUMOylation, a post-translational modificationmechanism. Here, we have identified a link betweenepithelial deSUMOylases and inflammation in IBD.DeSUMOylase SENP7 was seen to be upregulatedspecifically in intestinal epithelial cells in both humanIBD and a mouse model. In steady state, but not IBD,SENP7 expression was negatively regulated by adirect interaction and ubiquitination by SIAH2. Upre-gulated SENP7 in inflamed tissue displayed a distinctinteractome. These changes led to an expansion oflocalized proinflammatorygdT cells. Furthermore,in vivoknockdown of SENP7 or depletion ofgdT cells abrogated dextran sulfate sodium (DSS)-induced gut inflammation. Strong statistical correla-tions between upregulated SENP7 and high clinicaldisease indices were observed in IBD patients. Over-all, our data reveal that epithelial SENP7 is necessaryand sufficient for controlling gut inflammation, thushighlighting its importance as a potential drug target.

Item Type:	Article
Subjects:	Biomedical Science
Depositing User:	RCB Library
Date Deposited:	14 Mar 2023 09:44
Last Modified:	14 Mar 2023 09:44
URI:	http://rcb.sciencecentral.in/id/eprint/251

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