Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes

Chunfeng Qu, Emmerson W. Edwards, Frank Tacke, Véronique Angeli, Jaime Llodrá, Guzman Sanchez-Schmitz, Alexandre Garin, Nasreen S. Haque, Wendy Peters, Nico Van Rooijen, Carmen Sanchez-Torres, Jonathan Bromberg, Israel F. Charo, Steffen Jung, Sergio A. Lira, Gwendalyn J. Randolph

Research output: Contribution to journalArticle

234 Scopus citations

Abstract

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-1 int 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.

Original languageEnglish
Pages (from-to)1231-1241
Number of pages11
JournalJournal of Experimental Medicine
Volume200
Issue number10
DOIs
StatePublished - Nov 15 2004
Externally publishedYes

Keywords

  • Chemotaxis
  • Endothelium
  • Inflammation
  • Lymphatic system
  • Macrophage

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    Qu, C., Edwards, E. W., Tacke, F., Angeli, V., Llodrá, J., Sanchez-Schmitz, G., Garin, A., Haque, N. S., Peters, W., Van Rooijen, N., Sanchez-Torres, C., Bromberg, J., Charo, I. F., Jung, S., Lira, S. A., & Randolph, G. J. (2004). Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. Journal of Experimental Medicine, 200(10), 1231-1241. https://doi.org/10.1084/jem.20032152