Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis
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Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery. We engineered a murine microglia cell line, BV-2, to release EVs overexpressing the endogenous "eat me" signal Lactadherin (Mfg-e8) on the surface to target phagocytes and containing the anti-inflammatory cytokine IL-4. A single injection of 10 7 IL-4 + Mfg-e8 + EVs into the cisterna magna modulated established neuroinflammation and significantly reduced clinical signs in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Injected IL-4 + Mfg-e8 + EVs target mainly phagocytes (i.e., macrophages and microglia) surrounding liquoral spaces, and their cargo promote the upregulation of anti-inflammatory markers chitinase 3-like 3 (ym1) and arginase-1 (arg1), significantly reducing tissue damage. Engineered EVs may represent a biological drug delivery tool able to deliver multiple functional molecules simultaneously to treat neuroinflammatory diseases.
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Engineered exosomes loaded with IL-4 decreased experimental autoimmune encephalomyelitis score sharply and significantly reduced tissue damage.
“After applying the above exosomes, the experimental autoimmune encephalomyelitis score decreased sharply, significantly reducing tissue damage.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [83]
Engineered exosomes can deliver a variety of functional molecules to treat inflammatory diseases.
“The engineered exosomes can also deliver a variety of functional molecules to treat inflammatory diseases [83].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [83]
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- Authors
- Casella, G., Colombo, F., Finardi, A., Descamps, H., Ill-Raga, G., Spinelli, A., Podini, P., Bastoni, M., Martino, G., Muzio, L., & Furlan, R.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Corresponding author
- Furlan, Roberto
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 26
- Issue
- 9
- Pages
- 2107-2118
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC6127510
- OpenAlex
- W2814481017
- Cited by
- 134
- References
- 41
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 22 · 2023: 17 · 2022: 22 · 2021: 23 · 2020: 17 · 2019: 5 · 2018: 1 · 2016: 1
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Fondazione Italiana Sclerosi Multipla – FISM (2010/R/20)
- Merck
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, IL-4, neuroinflammation, multiple sclerosis, experimental autoimmune encephalomyelitis, microglia, MFG-E8, lactadherin, BV-2 cells, engineered vesicles, drug delivery, anti-inflammatory cytokines, Ym1, arginase-1, macrophages
- MeSH terms
- Extracellular Vesicles, Animals, Cell Line, Cells, Cultured, Disease Models, Animal, Female, Macrophages, Mice, Inbred C57BL, Microscopy, Fluorescence, Multiple Sclerosis, CD4-Positive T-Lymphocytes, Interleukin-4, Reverse Transcriptase Polymerase Chain Reaction, CD11b Antigen, Microscopy, Electron, Transmission, Mice, Rats
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