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PNAS 104 (20): 8421-8426

Copyright © 2007 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

A silent chemokine receptor regulates steady-state leukocyte homing in vivo

Kornelia Heinzel, Claudia Benz, and Conrad C. Bleul*

Department of Developmental Immunology, Max-Planck Institute of Immunobiology, Stübeweg 51, 79108 Freiburg, Germany

Edited by Jason Cyster, University of California, San Francisco, CA, and accepted by the Editorial Board February 3, 2007

Received for publication September 20, 2006.

Abstract: The location of leukocytes in different microenvironments is intimately connected to their function and, in the case of leukocyte precursors, to the executed differentiation and maturation program. Leukocyte migration within lymphoid organs has been shown to be mediated by constitutively expressed chemokines, but how the bioavailability of these homeostatic chemokines is regulated remains unknown. Here, we report in vivo evidence for the role of a nonsignaling chemokine receptor in the migration of leukocytes under physiological, i.e., noninflammatory, conditions. We have studied the in vivo role of the silent chemokine receptor CCX-CKR1 by both loss- and gain-of-function approaches. CCX-CKR1 binds the constitutively expressed chemokines CC chemokine ligand (CCL)19, CCL21, and CCL25. We find that CCX-CKR1 is involved in the steady-state homing of CD11c+MHCIIhigh dendritic cells to skin-draining lymph nodes, and it affects the homing of embryonic thymic precursors to the thymic anlage. These observations indicate that the silent chemokine receptor CCX-CKR1, which is exclusively expressed by stroma cells, but not hematopoietic cells themselves, regulates homeostatic leukocyte migration by controlling the availability of chemokines in the extracellular space. This finding adds another level of complexity to our understanding of leukocyte homeostatic migration.

Key Words: cell trafficking • homeostasis • lymphopoiesis • thymus

Author contributions: K.H., C.B., and C.C.B. designed research; K.H. and C.B. performed research; K.H., C.B., and C.C.B. analyzed data; and K.H., C.B., and C.C.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. J.C. is a guest editor invited by the Editorial Board.

This article contains supporting information online at www.pnas.org/cgi/content/full/0608274104/DC1.

*To whom correspondence should be addressed. E-mail: bleul{at}immunbio.mpg.de

© 2007 by The National Academy of Sciences of the USA

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