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Cutting Edge: The Orphan Chemokine Receptor G Protein-Coupled Receptor-2 (GPR-2, CCR10) Binds the Skin-Associated Chemokine CCL27 (CTACK/ALP/ILC)¹

Bernhard Homey^2,*, Wei Wang^2,*, Hortensia Soto^*, Matthew E. Buchanan^*, Andrea Wiesenborn, Daniel Catron^*, Anja Müller^*, Terrill K. McClanahan^*, Marie-Caroline Dieu-Nosjean, Rocio Orozco^§, Thomas Ruzicka, Percy Lehmann, Elizabeth Oldham^* and Albert Zlotnik^3,*

^* DNAX Research Institute, Palo Alto, CA 94304; Department of Dermatology, University of Düsseldorf, Düsseldorf, Germany; Schering Plough, Laboratory for Immunological Research, Dardilly, France; and ^§ Instituto Nacional de la Nutrición Salvador Zubirán, México City, México

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF- and IL-1ß. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.