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

Lymphatic exosomes promote dendritic cell migration along guidance cues.

Author information

1
Clinical Department of Pathology, Medical University of Vienna, Vienna, Austria.
2
Institute of Science and Technology, Klosterneuburg, Austria.
3
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, England, UK.
4
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
5
Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
6
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.
7
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
8
Institute of Science and Technology, Klosterneuburg, Austria Michael.sixt@ist.ac.at.
9
Clinical Department of Pathology, Medical University of Vienna, Vienna, Austria Dontscho.kerjaschki@meduniwien.ac.at.

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.

PMID:
29650776
PMCID:
PMC5987709
DOI:
10.1083/jcb.201612051
[Indexed for MEDLINE]
Free PMC Article

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