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GPR35 in Intestinal Diseases: From Risk Gene to Function.
Berna Kaya1, Hassan Melhem1, Jan Hendrik Niess1,2
1Department of Biomedicine, University of Basel, Basel, Switzerland.
Frontiers in Immunology
|November 18, 2021
Summary
G-protein coupled receptors (GPCRs) sense gut metabolites, influencing immune responses and intestinal health. Dysfunctional GPCR signaling, like that of GPR35, is linked to inflammatory bowel diseases (IBD).
Area of Science:
- Gastroenterology and Immunology
- Metabolomics and Receptor Signaling
Background:
- Diet and gut microbial metabolites are crucial for immune responses and intestinal homeostasis.
- Metabolite-sensing G-protein coupled receptors (GPCRs) link the immune system, gut microbiota, and metabolic processes.
- Inadequate GPCR signaling is implicated in diseases like inflammatory bowel diseases (IBD).
Purpose of the Study:
- To review the pharmacology of GPR35, a key GPCR in the intestine.
- To discuss GPR35's role in intestinal homeostasis and its association with IBD.
- To explore GPR35's endogenous and synthetic ligands, antagonists, and risk variants.
Main Methods:
- Literature review of studies on GPR35.
- Analysis of GPR35's pharmacology, including ligand interactions.
- Examination of GPR35 variants associated with gut diseases.
Main Results:
- GPR35 is activated by metabolites like kynurenic acid (KYNA) and lysophosphatidic acid (LPA) species.
- GPR35 is also activated by the chemokine CXCL17.
- GPR35 is identified as a risk gene for IBD, highlighting its significance in intestinal health.
Conclusions:
- GPR35 plays a critical role in mediating the link between gut metabolites, immune cells, and intestinal epithelial cells.
- Understanding GPR35's function and pharmacology is vital for developing therapeutic strategies for IBD and other gut-related diseases.
- Further research into GPR35's mechanisms can elucidate its contribution to intestinal homeostasis.
Keywords:
GPR35inflammatory bowel diseasesligand-receptor interactionsmetabolitesmicrobiotarisk variantsMore Related Videos
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