article published yes Michele Weber author 3A3FC708-F248-11E8-B48F-1D18A9856A87 Robert Hauschild author 4E01D6B4-F248-11E8-B48F-1D18A9856A870000-0001-9843-3522 Jan Schwarz author 346C1EC6-F248-11E8-B48F-1D18A9856A87 Christine Moussion author 3356F664-F248-11E8-B48F-1D18A9856A87 Ingrid De Vries author 4C7D837E-F248-11E8-B48F-1D18A9856A87 Daniel Legler author Sanjiv Luther author Mark Tobias Bollenbach author 3E6DB97A-F248-11E8-B48F-1D18A9856A870000-0003-4398-476X Michael K Sixt author 41E9FBEA-F248-11E8-B48F-1D18A9856A870000-0002-6620-9179 MiSi department Bio department Cytoskeletal force generation and force transduction of migrating leukocytes project Cell migration in complex environments: from in vivo experiments to theoretical models project 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. American Association for the Advancement of Science2013 eng 00031362200004710.1126/science.1228456 3396117328 - 332 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. <i>Science</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/science.1228456">https://doi.org/10.1126/science.1228456</a> 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.” <i>Science</i>. American Association for the Advancement of Science, 2013. <a href="https://doi.org/10.1126/science.1228456">https://doi.org/10.1126/science.1228456</a>. 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. M. Weber, R. Hauschild, J. Schwarz, C. Moussion, I. de Vries, D. Legler, S. Luther, M.T. Bollenbach, M.K. Sixt, Science 339 (2013) 328–332. Weber, Michele, et al. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” <i>Science</i>, vol. 339, no. 6117, American Association for the Advancement of Science, 2013, pp. 328–32, doi:<a href="https://doi.org/10.1126/science.1228456">10.1126/science.1228456</a>. Weber M, Hauschild R, Schwarz J, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. <i>Science</i>. 2013;339(6117):328-332. doi:<a href="https://doi.org/10.1126/science.1228456">10.1126/science.1228456</a> M. Weber <i>et al.</i>, “Interstitial dendritic cell guidance by haptotactic chemokine gradients,” <i>Science</i>, vol. 339, no. 6117. American Association for the Advancement of Science, pp. 328–332, 2013. 28392018-12-11T11:59:52Z2026-06-18T18:36:11Z