Lymphatic exosomes promote dendritic cell migration along guidance cues

J Cell Biol. 2018 Jun 4;217(6):2205-2221. doi: 10.1083/jcb.201612051. Epub 2018 Apr 12.

Abstract

Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Surface Extensions / metabolism
  • Cellular Microenvironment
  • Chemokine CX3CL1 / metabolism
  • Collagen / metabolism
  • Cues
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism*
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Humans
  • Inflammation / pathology
  • Kidney / metabolism
  • Kidney / pathology
  • Lymphatic Vessels / metabolism*
  • Male
  • Mice
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proteomics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Receptors, G-Protein-Coupled
  • Tumor Necrosis Factor-alpha
  • Collagen