title: 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.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and.
authors.forename: José L
authors.initials: JL
authors.lastname: Maravillas-Montero
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Burkhardt
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hevezi
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Carnevale
authors.affiliation: Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and Division of Medicinal Chemistry, Free University Amsterdam, 1081 HV Amsterdam, the Netherlands.
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Smit
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697; Institute for Immunology, University of California, Irvine, Irvine, CA 92697; and azlotnik@uci.edu.
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014162:Transfection
chemical_list: C508524:CXCL17 protein, human; C000591605:CXCL17 protein, mouse; D018925:Chemokines; D019743:Chemokines, CXC; C111379:GPR35 protein, human; D043562:Receptors, G-Protein-Coupled