Dataset Information

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

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.

SUBMITTER: Willis CM

PROVIDER: S-EPMC6535008 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Willis Cory M CM Nicaise Alexandra M AM Menoret Antoine A Ryu Jae Kyu JK Mendiola Andrew S AS Mendiola Andrew S AS Jellison Evan R ER Givogri Maria I MI Han David K DK Bongarzone Ernesto R ER Akassoglou Katerina K Vella Anthony T AT Crocker Stephen J SJ

Proceedings of the National Academy of Sciences of the United States of America 20190508 21

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<sub>35-55</sub>-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8+ T ce ...[more]

PMID: 31068461

Similar Datasets

Project description:The discovery of disease biomarkers, along with the use of "liquid biopsies" as a minimally invasive source of biomarkers, continues to be of great interest. In inflammatory diseases of the central nervous system (CNS), cerebrospinal fluid (CSF) is the most obvious biofluid source. Extracellular vesicles (EVs) are also present in CSF and are thought to be potential "biomarker treasure chests". However, isolating these CSF-derived EVs remains challenging. This small-scale pilot study developed and tested a protocol to enrich for CSF-EVs, both in relapsing remitting multiple sclerosis (RRMS) CSF and controls. These were subsequently compared, using an aptamer based proteomics array, SOMAscan™. EVs were enriched from RRMS patient (n = 4) and non-demyelinating control (idiopathic intracranial hypertension (IIH) (n = 3)) CSF using precipitation and mini size-exclusion chromatography (SEC). EV-enriched fractions were selected using pre-defined EV characteristics, including increased levels of tetraspanins. EVs and paired CSF were analysed by SOMAscan™, providing relative abundance data for 1128 proteins. CSF-EVs were characterised, revealing exosome-like features: rich in tetraspanins CD9 and CD81, size ~100 nm, and exosome-like morphology by TEM. Sufficient quantities of, SOMAscan™ compatible, EV material was obtained from 5 ml CSF for proteomics analysis. Overall, 348 and 580 proteins were identified in CSF-EVs and CSF, respectively, of which 50 were found to be significantly (t-test) and exclusively enriched in RRMS CSF-EVs. Selected proteins, Plasma kallikrein and Apolipoprotein-E4, were further validated by western blot and appeared increased in CSF-EVs compared to CSF. Functional enrichment analysis of the 50 enriched proteins revealed strong associations with biological processes relating to MS pathology and also extracellular regions, consistent with EV enrichment. This pilot study demonstrates practicality for EV enrichment in CSF derived from patients with MS and controls, allowing detailed analysis of protein profiles that may offer opportunities to identify novel biomarkers and therapeutic approaches in CNS inflammatory diseases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets