The Journal of Experimental Medicine
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Published online 8 November 2004 doi:10.1084/jem.20032152
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 10, 1231-1241
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Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes

Chunfeng Qu1, Emmerson W. Edwards1, Frank Tacke1, Véronique Angeli1, Jaime Llodrá1, Guzman Sanchez-Schmitz1,4, Alexandre Garin2, Nasreen S. Haque3, Wendy Peters5, Nico van Rooijen6, Carmen Sanchez-Torres4, Jonathan Bromberg1, Israel F. Charo5, Steffen Jung7, Sergio A. Lira2, and Gwendalyn J. Randolph1,2

1 Department of Gene and Cell Medicine, Mt. Sinai School of Medicine, New York, NY 10029
2 Center of Immunobiology, Mt. Sinai School of Medicine, New York, NY 10029
3 Department of Medicine, Mt. Sinai School of Medicine, New York, NY 10029
4 Department of Molecular Biomedicine, Center of Investigation and Advanced Studies CINVESTAV-IPN, Mexico City, Mexico 07360
5 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141
6 Department of Molecular Cell Biology, Free University Medical Center, Amsterdam 1081 BT, Netherlands
7 Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel

Address correspondence to Gwendalyn J. Randolph, Dept. of Gene and Cell Medicine and Center of Immunobiology, Mt. Sinai School of Medicine, Box 1496, 1425 Madison Ave., New York, NY 10029. Phone: (212) 659-8262; Fax: (212) 803-6740; email: Gwendalyn.Randolph{at}mssm.edu

Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX3CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX3CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1int monocyte population, and the number of latex+ DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1int monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1int monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.

Key Words: chemotaxis • endothelium • inflammation • lymphatic system • macrophage

Abbreviations used in this paper: CCR, chemokine receptor; LX, latex.


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