GPR35 in Intestinal Diseases: From Risk Gene to Function

^{Department of Biomedicine, University of Basel, Basel, Switzerland,}

^{Department of Gastroenterology/Hepatology, Clarunis - University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland,}

^{Corresponding author.}

Edited by: Oscar Gilberto Gomez-Duarte, University at Buffalo, United States

Reviewed by: Jochen Mattner, University Hospital Erlangen, Germany; Stefano Fiorucci, University of Perugia, Italy

*Correspondence: Jan Hendrik Niess, hc.sabinu@ssein.kirdnehnaj

This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

Edited by: Oscar Gilberto Gomez-Duarte, University at Buffalo, United States

Reviewed by: Jochen Mattner, University Hospital Erlangen, Germany; Stefano Fiorucci, University of Perugia, Italy

Received 2021 May 30; Accepted 2021 Oct 18.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Diet and gut microbial metabolites mediate host immune responses and are central to the maintenance of intestinal health. The metabolite-sensing G-protein coupled receptors (GPCRs) bind metabolites and trigger signals that are important for the host cell function, survival, proliferation and expansion. On the contrary, inadequate signaling of these metabolite-sensing GPCRs most likely participate to the development of diseases including inflammatory bowel diseases (IBD). In the intestine, metabolite-sensing GPCRs are highly expressed by epithelial cells and by specific subsets of immune cells. Such receptors provide an important link between immune system, gut microbiota and metabolic system. Member of these receptors, GPR35, a class A rhodopsin-like GPCR, has been shown to be activated by the metabolites tryptophan-derived kynurenic acid (KYNA), the chemokine CXCL17 and phospholipid derivate lysophosphatidic acid (LPA) species. There have been studies on GPR35 in the context of intestinal diseases since its identification as a risk gene for IBD. In this review, we discuss the pharmacology of GPR35 including its proposed endogenous and synthetic ligands as well as its antagonists. We elaborate on the risk variants of GPR35 implicated in gut-related diseases and the mechanisms by which GPR35 contribute to intestinal homeostasis.

Keywords: GPR35, microbiota, metabolites, ligand-receptor interactions, risk variants, inflammatory bowel diseases

Abstract

MAF, Minor Allele Frequency; UTR, Untranslated region.

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