4.8 Article

Extracellular vesicle fibrinogen induces encephalitogenic CD8+T cells in a mouse model of multiple sclerosis

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1816911116

关键词

autoimmunity; proteomics; EAE; T cell; relapse

资金

  1. National Institutes of Health (NIH) [R21NS087578, R56NS099359]
  2. NIH Shared Instrumentation Grant [NIH ODOD018034]
  3. National Institute of Neurological Diseases and Stroke Grant [R35NS097976]
  4. National Institute of Allergy and Infectious Disease [T32AI007334-29]
  5. American Heart Association Scientist Development Grant
  6. National Multiple Sclerosis Society Postdoctoral Fellowship [FG-1708-28925]
  7. Race to Erase MS Young Investigator Award

向作者/读者索取更多资源

Extracellular vesicles (EVs) are emerging as potent mediators of intercellular communication with roles in inflammation and disease. In this study, we examined the role of EVs from blood plasma (pEVs) in an experimental autoimmune encephalomyelitis mouse model of central nervous system demyelination. We determined that pEVs induced a spontaneous relapsing-remitting disease phenotype in MOG35-55-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8+ T cells and required fibrinogen in pEVs. Analysis of pEVs from relapsing-remitting multiple sclerosis patients also identified fibrinogen as a significant portion of pEV cargo. Together, these data suggest that fibrinogen in pEVs contributes to the perpetuation of neuroinflammation and relapses in disease.

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