Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis.
Cory M WillisAlexandra M NicaiseAntoine MenoretJae Kyu RyuAndrew S MendiolaEvan R JellisonMaria I GivogriDavid K HanErnesto R BongarzoneKaterina AkassoglouAnthony T VellaStephen J CrockerPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- multiple sclerosis
- mouse model
- white matter
- ejection fraction
- disease activity
- type diabetes
- oxidative stress
- newly diagnosed
- systemic lupus erythematosus
- electronic health record
- machine learning
- skeletal muscle
- metabolic syndrome
- rheumatoid arthritis
- lps induced
- prognostic factors
- insulin resistance
- stress induced