G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis

Boleij, A. et al. (2021) G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis. Communications Biology, 4, 585. (doi: 10.1038/s42003-021-02014-3) (PMID:33990686) (PMCID:PMC8121840)

Abstract

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jenkins, Mrs Laura and Milligan, Professor Graeme and MacKenzie, Dr Amanda
• Authors: Boleij, A., Fathi, P., Dalton, W., Park, B., Wu, X., Huso, D., Allen, J., Besharati, S., Anders, R. A., Housseau, F., Mackenzie, A. E., Jenkins, L., Milligan, G., Wu, S., and Sears, C. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Communications Biology
• Publisher: Nature Research
• ISSN: 2399-3642
• ISSN (Online): 2399-3642
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Communications Biology 4(1):585
• Publisher Policy: Reproduced under a Creative Commons licence