IBD-associated G protein-coupled receptor 65 variant compromises signalling and impairs key functions involved in inflammation.

ABSTRACT:

Background and aims

Inflammatory bowel diseases (IBD) result in chronic inflammation of the gastrointestinal tract. Genetic studies have shown that the GPR65 gene, as well as its missense coding variant, GPR65*Ile231Leu, is associated with IBD. We aimed to define the signalling and biological pathways downstream of GPR65 activation and evaluate the impact of GPR65*231Leu on these.

Methods

We used HEK 293 cells stably expressing GPR65 and deficient for either Gα_s, Gα_q/11 or Gα_12/13, to define GPR65 signalling pathways, IBD patient biopsies and a panel of human tissues, primary immune cells and cell lines to determine biologic context, and genetic modulation of human THP-1-derived macrophages to examine the impact of GPR65 in bacterial phagocyt

SUBMITTER: Mercier V 

PROVIDER: S-EPMC9536022 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature