4.7 Article

Lymphatic exosomes promote dendritic cell migration along guidance cues

期刊

JOURNAL OF CELL BIOLOGY
卷 217, 期 6, 页码 2205-2221

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201612051

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资金

  1. Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund
  2. Medizinische Universitat Wien
  3. European Research Council (ERC) [GA 281556]
  4. Austrian Science Fund START award
  5. Austrian Academy of Sciences
  6. Medical Research Council [G1100134, MR/L008610/1]
  7. Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung
  8. Advanced European Research Council grant LYVICAM
  9. Academy of Finland [287853]
  10. European Union [668036]
  11. [MC_UU_12010/2]
  12. Academy of Finland (AKA) [287853, 287853] Funding Source: Academy of Finland (AKA)
  13. Medical Research Council [MC_UU_12010/2, MR/L008610/1, 1093777, G1100134, MC_UU_00008/2, G1000800c, MC_U137884182, G0801186] Funding Source: researchfish
  14. MRC [MC_UU_00008/2, G0801186, MC_U137884182, MC_UU_12010/2, MR/L008610/1, G1100134] Funding Source: UKRI

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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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