Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Lymphatic Specific Disruption in the Fine Structure of Heparan Sulfate Inhibits Dendritic Cell Traffic and Functional T Cell Responses in the Lymph Node.
X. Yin, S. C. Johns, D. Kim, Z. Mikulski, C. L. Salanga, T. M. Handel, M. Macal, E. I. Zuniga, and M. M. Fuster (2014)
J. Immunol. 192, 2133-2142
   Abstract »    Full Text »    PDF »
Transendothelial migration of effector T cells across inflamed endothelial barriers does not require heparan sulfate proteoglycans.
L. Stoler-Barak, S. Barzilai, A. Zauberman, and R. Alon (2014)
Int. Immunol.
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors.
F. Bachelerie, A. Ben-Baruch, A. M. Burkhardt, C. Combadiere, J. M. Farber, G. J. Graham, R. Horuk, A. H. Sparre-Ulrich, M. Locati, A. D. Luster, et al. (2014)
Pharmacol. Rev. 66, 1-79
   Abstract »    Full Text »    PDF »
The chemokine CX3CL1 promotes trafficking of dendritic cells through inflamed lymphatics.
L. A. Johnson and D. G. Jackson (2013)
J. Cell Sci. 126, 5259-5270
   Abstract »    Full Text »    PDF »
Michael Sixt: Love the way they move.
C. Sedwick (2013)
J. Cell Biol. 202, 988-989
   Full Text »    PDF »
Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.
F. M. Coelho, D. Natale, S. F. Soriano, M. Hons, J. Swoger, J. Mayer, R. Danuser, E. Scandella, M. Pieczyk, H.-G. Zerwes, et al. (2013)
Blood 121, 4101-4109
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882