Lymphatic exosomes promote dendritic cell migration along guidance cues

• DOI: 10.1083/jcb.201612051
• Publication Date: 2018-04-12T12:35:18Z
• Authors: Markus Brown; Louise A. Johnson; Dario A. Leone; Peter Majek; Kari Vaahtomeri; Daniel Senfter; Nora Bukosza; Helga Schachner; Gabriele Asfour; Brigitte Langer; Robert Hauschild; Katja Parapatics; Young-Kwon Hong; Keiryn L. Bennett; Renate Kain; Michael Detmar; Michael Sixt; David G. Jackson; Dontscho Kerjaschki
• Keywords: EXPRESSION; Male; Proteomics; 0301 basic medicine; Exosomes; Kidney; Receptors, G-Protein-Coupled; Mice; 03 medical and health sciences; VESSELS; Cell Movement; Cell Line, Tumor; BREAST-CANCER; TRANSMIGRATION; Animals; Humans; Biochemistry, cell and molecular biology; Research Articles; Lymphatic Vessels; Inflammation; Chemokine CX3CL1; CHEMOKINE RECEPTOR CX3CR1; EXTRACELLULAR VESICLES; SAMPLE PREPARATION; Endothelial Cells; Prostatic Neoplasms; IN-VITRO; Dendritic Cells; ENDOTHELIAL-CELLS; Biomedicine; Cellular Microenvironment; Cell Surface Extensions; Collagen; Cues; CCL21

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.