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Updated: May 17, 2026
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
Claudia Verderio1, Luca Muzio, Elena Turola
1Italian National Research Council Institute of Neuroscience and Department of Medical Pharmacology, University of Milan, Milan, Italy. c.verderio@in.cnr.it
Objective:
Microvesicles (MVs) have been indicated as important mediators of intercellular communication and are emerging as new biomarkers of tissue damage. Our previous data indicate that reactive microglia/macrophages release MVs in vitro. The aim of the study was to evaluate whether MVs are released by microglia/macrophages in vivo and whether their number varies in brain inflammatory conditions, such as multiple sclerosis (MS).
Methods:
Electron and fluorescence microscopy and flow cytometry were used to detect myeloid MVs in the cerebrospinal fluid (CSF) of healthy controls, MS patients, and rodents affected by experimental autoimmune encephalomyelitis (EAE), the animal model of MS.
Results:
Myeloid MVs were detected in CSF of healthy controls. In relapsing and remitting EAE mice, the concentration of myeloid MVs in the CSF was significantly increased and closely associated with disease course. Analysis of MVs in the CSF of 28 relapsing patients and 28 patients with clinical isolated syndrome from 2 independent cohorts revealed higher levels of myeloid MVs than in 13 age-matched controls, indicating a clinical value of MVs as a companion tool to capture disease activity. Myeloid MVs were found to spread inflammatory signals both in vitro and in vivo at the site of administration; mice impaired in MV shedding were protected from EAE, suggesting a pathogenic role for MVs in the disease. Finally, FTY720, the first approved oral MS drug, significantly reduced the amount of MVs in the CSF of EAE-treated mice.
Interpretation:
These findings identify myeloid MVs as a marker and therapeutic target of brain inflammation.
Insights
Microglia/macrophage-derived microvesicles (MVs) are elevated in brain inflammation and multiple sclerosis (MS). These MVs play a pathogenic role and represent a potential therapeutic target for MS.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Biomarker Discovery
Background:
- Microvesicles (MVs) mediate intercellular communication and indicate tissue damage.
- Reactive microglia/macrophages are known to release MVs in vitro.
Purpose of the Study:
- To investigate MV release by microglia/macrophages in vivo.
- To determine if MV levels change in brain inflammatory conditions like multiple sclerosis (MS).
Main Methods:
- Detection of myeloid MVs in cerebrospinal fluid (CSF) using electron microscopy, fluorescence microscopy, and flow cytometry.
- Analysis in healthy controls, MS patients, and rodents with experimental autoimmune encephalomyelitis (EAE).
Main Results:
- Myeloid MVs were detected in the CSF of healthy controls and were significantly increased in EAE mice, correlating with disease severity.
- Elevated myeloid MVs were observed in MS patients and those with clinically isolated syndrome compared to controls.
- MVs demonstrated inflammatory signaling in vitro and in vivo; impaired MV shedding protected against EAE.
- The MS drug FTY720 reduced CSF MVs in EAE-treated mice.
Conclusions:
- Myeloid MVs are released by microglia/macrophages in vivo during brain inflammation.
- Myeloid MVs serve as a potential biomarker for brain inflammatory activity.
- Myeloid MVs represent a novel therapeutic target for inflammatory neurological diseases.
