Lymphatic exosomes promote dendritic cell migration along guidance cues

作者：Brown Markus; Johnson Louise A; Leone Dario A; Majek Peter; Vaahtomeri Kari; Senfter Daniel; Bukosza Nora; Schachner Helga; Asfour Gabriele; Langer Brigitte; Hauschild Robert; Parapatics Katja; Hong Young Kwon; Bennett Keiryn L; Kain Renate; Detmar Michael; Sixt Michael^*; Jackson David G; Kerjaschki Dontscho^*

来源：The Journal of Cell Biology, 2018, 217(6): 2205-2221.

DOI：10.1083/jcb.201612051

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.

• 出版日期2018-6