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Cutting edge: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17.

ABSTRACT: Chemokines are chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. Chemokines bind to G protein-coupled receptors expressed on target cells to initiate signaling cascades and induce chemotaxis. Although the cognate receptors of most chemokines have been identified, the receptor for the mucosal chemokine CXCL17 is undefined. In this article, we show that GPR35 is the receptor of CXCL17. GPR35 is expressed in mucosal tissues, in CXCL17-responsive monocytes, and in the THP-1 monocytoid cell line. Transfection of GPR35 into Ba/F3 cells rendered them responsive to CXCL17, as measured by calcium-mobilization assays. Furthermore, GPR35 expression is downregulated in the lungs of Cxcl17(-/-) mice, which exhibit defects in macrophage recruitment to the lungs. We conclude that GPR35 is a novel chemokine receptor and suggest that it should be named CXCR8.

SUBMITTER: Maravillas-Montero JL

PROVIDER: S-EPMC4355404 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Cutting edge: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17.

Maravillas-Montero José L JL Burkhardt Amanda M AM Hevezi Peter A PA Carnevale Christina D CD Smit Martine J MJ Zlotnik Albert A

Journal of immunology (Baltimore, Md. : 1950) 20141119 1

Chemokines are chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. Chemokines bind to G protein-coupled receptors expressed on target cells to initiate signaling cascades and induce chemotaxis. Although the cognate receptors of most chemokines have been identified, the receptor for the mucosal chemokine CXCL17 is undefined. In this article, we show that GPR35 is the receptor of CXCL17. GPR35 is expressed in mucosal tissues, in CXCL17-responsive monocytes, and ...[more]

PMID: 25411203

Similar Datasets

GPR35 mediates lodoxamide-induced migration inhibitory response but not CXCL17-induced migration stimulatory response in THP-1 cells; is GPR35 a receptor for CXCL17?

Project description:Background and purposeGPR35 has long been considered an orphan GPCR, because no endogenous ligand of GPR35 has been discovered. CXCL17 (a chemokine) has been reported to be an endogenous ligand of GPR35, and it has even been suggested that it be called CXCR8. However, at present there is no supporting evidence that CXCL17 does interact with GPR35.Experimental approachWe applied two assay systems to explore the relationship between CXCL17 and GPR35. An AP-TGF-α shedding assay in GPR35 over-expressing HEK293 cells was used as a gain-of-function assay. GPR35 knock-down by siRNA transfection was performed in endogenously GPR35-expressing THP-1 cells.Key resultsIn the AP-TGF-α shedding assay, lodoxamide, a well-known synthetic GPR35 agonist, was confirmed to be the most potent agonist among other reported agonists. However, neither human nor mouse CXCL17 had an effect on GPR35. Consistent with previous findings, G proteins Gαi/o and Gα12/13 were found to couple with GPR35. Furthermore, lodoxamide-induced activation of GPR35 was concentration-dependently inhibited by CID2745687 (a selective GPR35 antagonist). In endogenously GPR35-expressing THP-1 cells, lodoxamide concentration-dependently inhibited migration and this inhibitory effect was blocked by CID2745687 treatment or GPR35 siRNA transfection. However, even though CXCL17 stimulated the migration of THP-1 cells, which is consistent with a previous report, this stimulatory effect of CXCL17 was not blocked by CID2745687 or GPR35 siRNA.Conclusions and implicationsThe present findings suggest that GPR35 functions as a migration inhibitory receptor, but CXCL17-stimulated migration of THP-1 cells is not dependent on GPR35.

| S-EPMC5740256 | biostudies-literature

CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity.

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Involvement of CXCL17 and GPR35 in Gastric Cancer Initiation and Progression.

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CXCL17: The Black Sheep in the Chemokine Flock.

Project description: Not available

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Cutting edge: lung mucosal Th17-mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels.

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| S-EPMC2740792 | biostudies-literature

Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage.

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Cutting Edge: Aire Is a Coactivator of the Vitamin D Receptor.

Project description:Vitamin D deficiency is associated with the development of autoimmunity, which arises from defects in T cell tolerance to self-antigens. Interactions of developing T cells with medullary thymic epithelial cells, which express tissue-restricted Ags, are essential for the establishment of central tolerance. However, vitamin D signaling in the thymus is poorly characterized. We find that stromal and hematopoietic cells in the mouse thymus express the vitamin D receptor (Vdr) and Cyp27b1, the enzyme that produces hormonal 1,25-dihydroxyvitamin D (1,25D). Treatment of cultured thymic slices with 1,25D enhances expression of the critical medullary thymic epithelial cell transcription factor autoimmune regulator (Aire), its colocalization with the Vdr, and enhances tissue-restricted Ag gene expression. Moreover, the Vdr interacts with Aire in a 1,25D-dependent manner and recruits Aire to DNA at vitamin D response elements, where it acts as a Vdr coactivator. These data link vitamin D signaling directly to critical transcriptional events necessary for central tolerance.

| S-EPMC10315440 | biostudies-literature

Ectopic expression of the chemokine CXCL17 in colon cancer cells.

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