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Publication : Interstitial dendritic cell guidance by haptotactic chemokine gradients.

First Author  Weber M Year  2013
Journal  Science Volume  339
Issue  6117 Pages  328-32
PubMed ID  23329049 Mgi Jnum  J:193398
Mgi Id  MGI:5468368 Doi  10.1126/science.1228456
Citation  Weber M, et al. (2013) Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339(6117):328-32
abstractText  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.
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