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Science 339 (6117): 328-332

Copyright © 2013 by the American Association for the Advancement of Science

Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients

Michele Weber,1 Robert Hauschild,1 Jan Schwarz,1 Christine Moussion,1 Ingrid de Vries,1 Daniel F. Legler,2 Sanjiv A. Luther,3 Tobias Bollenbach,1 Michael Sixt1,*

Abstract: 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.

1 IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria.
2 Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Unterseestrasse 47, CH-8280 Kreuzlingen, Switzerland.
3 Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.

* To whom correspondence should be addressed. E-mail: Sixt{at}ist.ac.at

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