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A CFSE-based Assay to Study the Migration of Murine Skin Dendritic Cells into Draining Lymph Nodes During Infection with Mycobacterium bovis Bacille Calmette-Guérin
07:14

A CFSE-based Assay to Study the Migration of Murine Skin Dendritic Cells into Draining Lymph Nodes During Infection with Mycobacterium bovis Bacille Calmette-Guérin

Published on: October 9, 2016

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

Orna Tal1, Hwee Ying Lim, Irina Gurevich

  • 1Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.

The Journal of Experimental Medicine
|September 21, 2011
PubMed

Insights

Skin inflammation mobilizes dendritic cells (DCs) to migrate towards lymphatics. The CCL21-CCR7 axis is crucial for DC chemotaxis and transmigration into lymphatic vessels for immune surveillance.

Area of Science:

  • Immunology
  • Cell Biology
  • Lymphatic System Dynamics

Background:

  • Dendritic cells (DCs) are essential for initiating immune responses by migrating from tissues to lymph nodes.
  • The precise mechanisms governing DC mobilization, transmigration through lymphatic endothelium, and intralymphatic movement remain incompletely understood.

Purpose of the Study:

  • To investigate the in vivo dynamics of dendritic cell migration in response to skin inflammation.
  • To elucidate the role of the CCL21-CCR7 axis in dendritic cell trafficking and lymphatic entry.

Main Methods:

  • Live mouse imaging to observe dendritic cell behavior in inflamed skin and initial lymphatics.
  • Analysis of wild-type and CCR7-deficient bone marrow-derived dendritic cells (BMDCs) during migration.
  • Characterization of CCL21 distribution on the lymphatic basement membrane.

Main Results:

  • Skin inflammation significantly increases interstitial motility of dermal DCs.
  • Activated DCs migrate directionally towards lymphatics, interacting with CCL21 deposits to transmigrate.
  • CCR7-deficient DCs exhibit impaired docking and transmigration into lymphatics despite random migration towards them.
  • Intralymphatic crawling, guided by lymph flow and adhesion, facilitates DC movement within lymphatic vessels before reaching collecting lymphatics.

Conclusions:

  • The CCL21-CCR7 axis plays a dual role, promoting DC chemotaxis and anchoring them to lymphatic endothelium for transmigration.
  • Intralymphatic crawling represents a novel mechanism of DC mobilization, integrating active migration with lymph flow cues.
  • These findings offer potential targets for regulating immune cell trafficking.

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