PMID- 21930767
OWN - NLM
STAT- MEDLINE
DCOM- 20111114
LR  - 20211020
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 208
IP  - 10
DP  - 2011 Sep 26
TI  - DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic 
      endothelium and intralymphatic crawling.
PG  - 2141-53
LID - 10.1084/jem.20102392 [doi]
AB  - Dendritic cells (DCs) must travel through lymphatics to carry skin antigens into 
      lymph nodes. The processes controlling their mobilization and migration have not 
      been completely delineated. We studied how DCs in live mice respond to skin 
      inflammation, transmigrate through lymphatic endothelium, and propagate in 
      initial lymphatics. At steady state, dermal DCs remain sessile along blood 
      vessels. Inflammation mobilizes them, accelerating their interstitial motility 
      2.5-fold. CCR7-deficient BMDCs crawl as fast as wild-type DCs but less 
      persistently. We observed discrete depositions of CCL21 complexed with 
      collagen-IV on the basement membrane of initial lymphatics. Activated DCs move 
      directionally toward lymphatics, contact CCL21 puncta, and migrate through 
      portals into the lumen. CCR7-deficient DCs arrive at lymphatics through random 
      migration but fail to dock and transmigrate. Once inside vessels, wild-type DCs 
      use lamellipodia to crawl along lymphatic endothelium and, sensing lymph flow, 
      proceed downstream. DCs start drifting freely only in collecting lymphatics. 
      These results demonstrate in vivo that the CCL21-CCR7 axis plays a dual role in 
      DC mobilization: promoting both chemotaxis and arrest of DCs on lymphatic 
      endothelium. Intralymphatic crawling, in which DCs combine active adhesion-based 
      migration and directional cues from lymph flow, represents a new step in DC 
      mobilization which may be amenable to regulation.
FAU - Tal, Orna
AU  - Tal O
AD  - Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
FAU - Lim, Hwee Ying
AU  - Lim HY
FAU - Gurevich, Irina
AU  - Gurevich I
FAU - Milo, Idan
AU  - Milo I
FAU - Shipony, Zohar
AU  - Shipony Z
FAU - Ng, Lai Guan
AU  - Ng LG
FAU - Angeli, Veronique
AU  - Angeli V
FAU - Shakhar, Guy
AU  - Shakhar G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110919
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Chemokine CCL21)
RN  - 0 (Receptors, CCR7)
SB  - IM
MH  - Animals
MH  - Cell Movement/*immunology
MH  - Chemokine CCL21/*immunology
MH  - Dendritic Cells/cytology/*immunology/*physiology
MH  - Endothelium, Lymphatic/*immunology
MH  - Foot
MH  - Inflammation/immunology
MH  - Injections, Intralymphatic
MH  - Lymph Nodes/cytology/*immunology
MH  - Lymphatic Vessels/cytology/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, CCR7/immunology
MH  - Signal Transduction/immunology
MH  - Skin/*cytology/immunology
PMC - PMC3182054
EDAT- 2011/09/21 06:00
MHDA- 2011/11/15 06:00
PMCR- 2012/03/26
CRDT- 2011/09/21 06:00
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2011/11/15 06:00 [medline]
PHST- 2012/03/26 00:00 [pmc-release]
AID - jem.20102392 [pii]
AID - 20102392 [pii]
AID - 10.1084/jem.20102392 [doi]
PST - ppublish
SO  - J Exp Med. 2011 Sep 26;208(10):2141-53. doi: 10.1084/jem.20102392. Epub 2011 Sep 
      19.