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.
German Research Foundation (Si1323-1,2 to M.S.),
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Weber M, Hauschild R, Schwarz J, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 2013;339(6117):328-332. doi:10.1126/science.1228456
Weber, M., Hauschild, R., Schwarz, J., Moussion, C., De Vries, I., Legler, D., … Sixt, M. K. (2013). Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science, 339(6117), 328–332. https://doi.org/10.1126/science.1228456
Weber, Michele, Robert Hauschild, Jan Schwarz, Christine Moussion, Ingrid De Vries, Daniel Legler, Sanjiv Luther, Mark Tobias Bollenbach, and Michael K Sixt. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science 339, no. 6117 (2013): 328–32. https://doi.org/10.1126/science.1228456.
M. Weber et al., “Interstitial dendritic cell guidance by haptotactic chemokine gradients,” Science, vol. 339, no. 6117, pp. 328–332, 2013.
Weber M, Hauschild R, Schwarz J, Moussion C, De Vries I, Legler D, Luther S, Bollenbach MT, Sixt MK. 2013. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 339(6117), 328–332.
Weber, Michele, et al. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science, vol. 339, no. 6117, American Association for the Advancement of Science, 2013, pp. 328–32, doi:10.1126/science.1228456.