Dendritic Cells Enter Lymph Vessels by Hyaluronan-Mediated Docking to the Endothelial Receptor LYVE-1

Nat Immunol. 2017 Jul;18(7):762-770. doi: 10.1038/ni.3750. Epub 2017 May 15.

Abstract

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.

MeSH terms

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

Substances

  • Glycoproteins
  • LYVE1 protein, human
  • Membrane Transport Proteins
  • Vesicular Transport Proteins
  • Xlkd1 protein, mouse
  • Hyaluronic Acid