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

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...

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Autores principales: Willis, Cory M., Nicaise, Alexandra M., Menoret, Antoine, Ryu, Jae Kyu, Mendiola, Andrew S., Jellison, Evan R., Givogri, Maria I., Han, David K., Bongarzone, Ernesto R., Akassoglou, Katerina, Vella, Anthony T., Crocker, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535008/
https://www.ncbi.nlm.nih.gov/pubmed/31068461
http://dx.doi.org/10.1073/pnas.1816911116
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author Willis, Cory M.
Nicaise, Alexandra M.
Menoret, Antoine
Ryu, Jae Kyu
Mendiola, Andrew S.
Jellison, Evan R.
Givogri, Maria I.
Han, David K.
Bongarzone, Ernesto R.
Akassoglou, Katerina
Vella, Anthony T.
Crocker, Stephen J.
author_facet Willis, Cory M.
Nicaise, Alexandra M.
Menoret, Antoine
Ryu, Jae Kyu
Mendiola, Andrew S.
Jellison, Evan R.
Givogri, Maria I.
Han, David K.
Bongarzone, Ernesto R.
Akassoglou, Katerina
Vella, Anthony T.
Crocker, Stephen J.
author_sort Willis, Cory M.
collection PubMed
description 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 MOG(35–55)-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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spelling pubmed-65350082019-06-03 Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis Willis, Cory M. Nicaise, Alexandra M. Menoret, Antoine Ryu, Jae Kyu Mendiola, Andrew S. Jellison, Evan R. Givogri, Maria I. Han, David K. Bongarzone, Ernesto R. Akassoglou, Katerina Vella, Anthony T. Crocker, Stephen J. Proc Natl Acad Sci U S A Biological Sciences 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 MOG(35–55)-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. National Academy of Sciences 2019-05-21 2019-05-08 /pmc/articles/PMC6535008/ /pubmed/31068461 http://dx.doi.org/10.1073/pnas.1816911116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Willis, Cory M.
Nicaise, Alexandra M.
Menoret, Antoine
Ryu, Jae Kyu
Mendiola, Andrew S.
Jellison, Evan R.
Givogri, Maria I.
Han, David K.
Bongarzone, Ernesto R.
Akassoglou, Katerina
Vella, Anthony T.
Crocker, Stephen J.
Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title_full Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title_fullStr Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title_full_unstemmed Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title_short Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis
title_sort extracellular vesicle fibrinogen induces encephalitogenic cd8+ t cells in a mouse model of multiple sclerosis
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535008/
https://www.ncbi.nlm.nih.gov/pubmed/31068461
http://dx.doi.org/10.1073/pnas.1816911116
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