The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/165/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 1, July 7, 1997 165-170

Brief Definitive Reports

Identification of CCR8: A Human Monocyte and Thymus Receptor for the CC Chemokine I-309

H. Lee Tiffany*, Laura L. Lautens{ddagger}, Ji-Liang Gao*, James Pease*,||, Massimo Locati*, Christophe Combadiere*, William Modi, Tom I. Bonner{ddagger},§, and Philip M. Murphy*

From the * Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the {ddagger} Laboratory of Cell Biology and § Section on Genetics, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892; || the Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom; the Biological Carcinogenesis and Development Program, Program Resources, Incorporated/Dyncorp, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201

The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1. After transfection with the CY6 open reading frame, a mouse pre–B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous I-309 receptors expressed in an HL-60 clone 15 cell line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine receptors. CCR8 may regulate monocyte chemotaxis and thymic cell line apoptosis.

M. Locati is a recipient of a fellowship from the Italian Association for Cancer Research.

Address corespondence to Philip M. Murphy, M.D., Building 10, Room 11N113, National Institutes of Health, Bethesda, MD 20892. Phone: 301-496-2877; FAX: 301-402-4369; E-mail: pmm{at}nih.gov; or Tom I. Bonner, Ph.D. Building 36, Room 7A07, National Institutes of Health, Bethesda, MD 20892. Phone: 301-496-8906; FAX: 301-402-1748; E-mail: tibonner{at}helix.nih.gov


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