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.
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7 July 1997
Brief Definitive Report|
July 07 1997
Identification of CCR8: A Human Monocyte and Thymus Receptor for the CC Chemokine I-309
H. Lee Tiffany,
H. Lee Tiffany
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Laura L. Lautens,
Laura L. Lautens
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Ji-Liang Gao,
Ji-Liang Gao
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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James Pease,
James Pease
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Massimo Locati,
Massimo Locati
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Christophe Combadiere,
Christophe Combadiere
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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William Modi,
William Modi
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Tom I. Bonner,
Tom I. Bonner
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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Philip M. Murphy
Philip M. Murphy
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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H. Lee Tiffany
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Laura L. Lautens
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Ji-Liang Gao
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
James Pease
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Massimo Locati
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Christophe Combadiere
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
William Modi
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Tom I. Bonner
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
Philip M. Murphy
From the *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, and the ‡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
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: [email protected]; 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: [email protected]
Received:
April 02 1997
Revision Received:
April 23 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (1): 165–170.
Article history
Received:
April 02 1997
Revision Received:
April 23 1997
Citation
H. Lee Tiffany, Laura L. Lautens, Ji-Liang Gao, James Pease, Massimo Locati, Christophe Combadiere, William Modi, Tom I. Bonner, Philip M. Murphy; Identification of CCR8: A Human Monocyte and Thymus Receptor for the CC Chemokine I-309. J Exp Med 7 July 1997; 186 (1): 165–170. doi: https://doi.org/10.1084/jem.186.1.165
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