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.
This work was supported by National Institute of Allergic and Infectious Disease/National Institutes of Health Grant R01AI093548. J.L.M.-M. was supported by a University of California Institute for Mexico and the United States Postdoctoral Fellowship.
The online version of this article contains supplemental material.
- Received July 16, 2014.
- Accepted October 27, 2014.
- Copyright © 2014 by The American Association of Immunologists, Inc.