Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients

Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-01, Vol.339 (6117), p.328-332
Main Authors: Weber, Michele, Hauschild, Robert, Schwarz, Jan, Moussion, Christine, de Vries, Ingrid, Legler, Daniel F., Luther, Sanjiv A., Bollenbach, Tobias, Sixt, Michael
Format: Article
Language:English
Subjects:
Animals
Cellular biology
Chemokine CCL19 - metabolism
Chemokine CCL21 - chemistry
Chemokine CCL21 - immunology
Chemokines
Chemotaxis - immunology
Dendritic cells
Dendritic Cells - immunology
Dermis
Disruption
Ear
Embryology
Endothelial cells
Heparitin Sulfate - chemistry
Immobilized Proteins - chemistry
Immobilized Proteins - immunology
Immunity
Incubation
Interstitials
Lymphatic Vessels - immunology
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Migration
Movements
Movies
Quantification
Receptors, CCR7 - genetics
Signals
Skin - immunology
Sulfates
Tracking
Vessels
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Summary:Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1228456