Thursday, 21 June 2018 09:53

Lymphatic exosomes promote dendritic cell migration along guidance cues

doi:  10.1083/jcb.201612051

 

Markus Brown,1,2 Louise A. Johnson,3 Dario A. Leone,1 Peter Majek,4 Kari Vaahtomeri,2 Daniel Senfter,5 Nora Bukosza,1 Helga Schachner,1 Gabriele Asfour,1 Brigitte Langer,1 Robert Hauschild,2 Katja Parapatics,4 Young-Kwon Hong,6 Keiryn L. Bennett,4 Renate Kain,1 Michael Detmar,7 Michael Sixt,2 David G. Jackson,3 Dontscho Kerjaschki1


1Clinical Department of Pathology, Medical University of Vienna, Vienna, Austria
2Institute of Science and Technology, Klosterneuburg, Austria
3Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
4CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
5Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
6Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
7Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland

 

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.