Lymphatic exosomes promote dendritic cell migration along guidance cues.
Lymphatic exosomes promote dendritic cell migration along guidance cues.
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DOI：
10.1083/jcb.201612051
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发表时间：
2018-06-04
期刊：
影响因子：
--
通讯作者：
Kerjaschki D
中科院分区：
文献类型：
--
作者：
Brown M;Johnson LA;Leone DA;Majek P;Vaahtomeri K;Senfter D;Bukosza N;Schachner H;Asfour G;Langer B;Hauschild R;Parapatics K;Hong YK;Bennett KL;Kain R;Detmar M;Sixt M;Jackson DG;Kerjaschki D
Inflammation stimulates lymphatic endothelial cells to release exosomes, which accumulate in the perivascular stroma. Brown et al. show that these exosomes promote the directional migration of dendritic cells along guidance cues in complex environments by enhancing dynamic cellular protrusions in a CX3CL1-dependent manner. 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.
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