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GPR35 in Intestinal Diseases: From Risk Gene to Function

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 expansi...

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Autores principales: Kaya, Berna, Melhem, Hassan, Niess, Jan Hendrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591220/
https://www.ncbi.nlm.nih.gov/pubmed/34790192
http://dx.doi.org/10.3389/fimmu.2021.717392
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author Kaya, Berna
Melhem, Hassan
Niess, Jan Hendrik
author_facet Kaya, Berna
Melhem, Hassan
Niess, Jan Hendrik
author_sort Kaya, Berna
collection PubMed
description 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.
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spelling pubmed-85912202021-11-16 GPR35 in Intestinal Diseases: From Risk Gene to Function Kaya, Berna Melhem, Hassan Niess, Jan Hendrik Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-01 /pmc/articles/PMC8591220/ /pubmed/34790192 http://dx.doi.org/10.3389/fimmu.2021.717392 Text en Copyright © 2021 Kaya, Melhem and Niess https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Kaya, Berna
Melhem, Hassan
Niess, Jan Hendrik
GPR35 in Intestinal Diseases: From Risk Gene to Function
title GPR35 in Intestinal Diseases: From Risk Gene to Function
title_full GPR35 in Intestinal Diseases: From Risk Gene to Function
title_fullStr GPR35 in Intestinal Diseases: From Risk Gene to Function
title_full_unstemmed GPR35 in Intestinal Diseases: From Risk Gene to Function
title_short GPR35 in Intestinal Diseases: From Risk Gene to Function
title_sort gpr35 in intestinal diseases: from risk gene to function
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591220/
https://www.ncbi.nlm.nih.gov/pubmed/34790192
http://dx.doi.org/10.3389/fimmu.2021.717392
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