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Trafficking of tissue dendritic cells (DCs) via lymph is critical for the generation of cellular immune responses in draining lymph nodes (LNs). In the current study we found that DCs docked to the basolateral surface of lymphatic vessels and transited to the lumen through hyaluronan-mediated interactions with the lymph-specific endothelial receptor LYVE-1, in dynamic transmigratory-cup-like structures. Furthermore, we show that targeted deletion of the gene Lyve1, antibody blockade or depletion of the DC hyaluronan coat not only delayed lymphatic trafficking of dermal DCs but also blunted their capacity to prime CD8(+) T cell responses in skin-draining LNs. Our findings uncovered a previously unknown function for LYVE-1 and show that transit through the lymphatic network is initiated by the recognition of leukocyte-derived hyaluronan.

Original publication

DOI

10.1038/ni.3750

Type

Journal article

Journal

Nat Immunol

Publication Date

07/2017

Volume

18

Pages

762 - 770

Keywords

Animals, Cell Movement, Dendritic Cells, Endothelial Cells, Endothelium, Lymphatic, Flow Cytometry, Glycoproteins, Humans, Hyaluronic Acid, Immunity, Cellular, Lymph Nodes, Lymphatic Vessels, Mice, Mice, Knockout, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Vesicular Transport Proteins