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Proc Natl Acad Sci U S A. 2019 May 21;116(21):10488-10493. doi: 10.1073/pnas.1816911116. Epub 2019 May 8.

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

Author information

1
Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030.
2
Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030.
3
Institute for Systems Genomics, UConn Health, Farmington, CT 06030.
4
Gladstone Institute of Neurological Disease, San Francisco, CA 94158.
5
Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612.
6
Department of Cell Biology, University of Connecticut School of Medicine, Farmington, CT 06030.
7
Department of Neurology, University of California, San Francisco, CA 94143.
8
Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06030; crocker@uchc.edu.

Abstract

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.

KEYWORDS:

EAE; T cell; autoimmunity; proteomics; relapse

Conflict of interest statement

Conflict of interest statement: K.A. is a scientific cofounder of MedaRed, Inc. Her interests are managed by the Gladstone Institutes in accordance with its conflict of interest policy.

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