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CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3 and Is Highly Expressed in Human Dendritic Cells

David R. Greaves^*, Wei Wang^||, Daniel J. Dairaghi^,||, Marie Caroline Dieu, Blandine de Saint-Vis, Karin Franz-Bacon^||, Devora Rossi^||, Christophe Caux, Terrill McClanahan^||, Siamon Gordon^*, Albert Zlotnik^||, and Thomas J. Schall^||,

From the ^* Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; Schering-Plough Laboratory for Immunological Research, Dardilly 69571, France; Molecular Medicine Research Institute, Mountain View, California 94043; and ^|| The DNAX Research Institute, Palo Alto, California 94304

Dendritic cells initiate immune responses by ferrying antigen from the tissues to the lymphoid organs for presentation to lymphocytes. Little is known about the molecular mechanisms underlying this migratory behavior. We have identified a chemokine receptor which appears to be selectively expressed in human dendritic cells derived from CD34⁺ cord blood precursors, but not in dendritic cells derived from peripheral blood monocytes. When stably expressed as a recombinant protein in a variety of host cell backgrounds, the receptor shows a strong interaction with only one chemokine among 25 tested: the recently reported CC chemokine macrophage inflammatory protein 3. Thus, we have designated this receptor as the CC chemokine receptor 6. The cloning and characterization of a dendritic cell CC chemokine receptor suggests a role for chemokines in the control of the migration of dendritic cells and the regulation of dendritic cell function in immunity and infection.

DNAX is supported by Schering-Plough; work in the laboratory of S. Gordon is supported by the United Kingdom Medical Research Council; D.R. Greaves is supported by Glaxo Wellcome.

¹ Abbreviations used in this paper: CCR, a receptor for CC chemokines; CHO, Chinese hamster ovary; CXCR, a receptor for CXC chemokines; DC, dendritic cell; HEK293, human embryonic kidney 293; IC2, second intracellular loop; LARC, liver activation–related chemokine; MIP, macrophage inflammatory protein; mRNA, messenger RNA; ORF, open reading frame; TM, transmembrane.

D.R. Greaves and W. Wang contributed equally to this study.

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