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Cited by 269Lymphatic System and DiseasesChemokine receptors and signalingImmunotherapy and Immune Responses

DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling

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Tal, Orna, Lim, Hwee Ying, Gurevich, Irina, Milo, Idan, Shipony, Zohar, Ng, Lai Guan, Angeli, Veronique, Shakhar, Guy·2011·Journal of Experimental Medicine
DOI 10.1084/jem.20102392PMC PMC3182054
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Abstract

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.

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  • Once immunocytes access initial LVs, they crawl on the LEC luminal surface, initially randomly and thereafter in the direction of the lymph node.

    “Once immunocytes access initial LVs, they crawl on the LEC luminal surface (99, 114, 120) ( Figure 3a ). Crawling is initially random, but thereafter it is in the direction of the lymph node.”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [120]

    The Results section ('The mode of DC propagation in initial lymphatics is active crawling'; page not available) reports that dendritic cells crawl along luminal surfaces, sometimes moving back and forth, and become more directionally persistent toward the lymph node when flow is increased. It does not establish an inevitable progression from random to directed crawling after entry, or demonstrate that pattern for immunocytes generally. (LLM, conf=0.84)

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Authors
Tal, O., Lim, H. Y., Gurevich, I., Milo, I., Shipony, Z., Ng, L. G., Angeli, V., & Shakhar, G.
Affiliations
  • Weizmann Institute of Science (IL)
  • National University of Singapore (SG)
  • Agency for Science, Technology and Research (SG)
  • Department of Microbiology, Immunology Programme, Yoon Loo Lin School of Medicine, National University of Singapore, Singapore, 117456 2
Corresponding author
Shakhar, Guy
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2011-09-19
Volume
208
Issue
10
Pages
2141-2153
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20102392
PMC
PMC3182054
OpenAlex
W2006123588
Cited by
269
References
1
Citations by year
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FWCI
10.72
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
dendritic cell mobilization, CCL21, CCR7, lymphatic endothelium, skin inflammation, chemotaxis, lamellipodia, lymph flow, dermal dendritic cells
MeSH terms
Animals, Cell Movement, Dendritic Cells, Endothelium, Lymphatic, Foot, Inflammation, Injections, Intralymphatic, Lymph Nodes, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Skin, Signal Transduction, Lymphatic Vessels, Mice, Receptors, CCR7, Chemokine CCL21

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