title: Interstitial dendritic cell guidance by haptotactic chemokine gradients.
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.
authors: IST Austria (Institute of Science and Technology Austria), Klosterneuburg, Austria.
authors: Michele
authors: M
authors: Weber
authors: Robert
authors: R
authors: Hauschild
authors: Jan
authors: J
authors: Schwarz
authors: Christine
authors: C
authors: Moussion
authors: Ingrid
authors: I
authors: de Vries
authors: Daniel F
authors: DF
authors: Legler
authors: Sanjiv A
authors: SA
authors: Luther
authors: Tobias
authors: T
authors: Bollenbach
authors: Michael
authors: M
authors: Sixt
mesh_terms: D000818:Animals; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000737:chemistry / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006497:Heparan Sulfate / Q000737:chemistry; D055767:Immobilized Proteins / Q000737:chemistry / Q000276:immunology; D042601:Lymphatic Vessels / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D054400:Receptors, CCR7 / Q000235:genetics; D012867:Skin / Q000276:immunology*
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D006497:Heparan Sulfate; D055767:Immobilized Proteins; D054400:Receptors, CCR7; C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse