Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes.
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.
Qu
Chunfeng
C
Dept. of Gene and Cell Medicine, Mt. Sinai School of Medicine, Box 1496, 1425 Madison Ave., New York, NY 10029, USA.
Edwards
Emmerson W
EW
Tacke
Frank
F
Angeli
Véronique
V
Llodrá
Jaime
J
Sanchez-Schmitz
Guzman
G
Garin
Alexandre
A
Haque
Nasreen S
NS
Peters
Wendy
W
van Rooijen
Nico
N
Sanchez-Torres
Carmen
C
Bromberg
Jonathan
J
Charo
Israel F
IF
Jung
Steffen
S
Lira
Sergio A
SA
Randolph
Gwendalyn J
GJ
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009000:Monocytes / Q000166:cytology*; D054400:Receptors, CCR7; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology
C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; C489319:Ccr8 protein, mouse; D016207:Cytokines; D017931:DNA Primers; D054400:Receptors, CCR7; D054401:Receptors, CCR8; D019707:Receptors, Chemokine