Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis

Autor: Paola Podini, Gerard Ill-Raga, Mattia Bastoni, Gianvito Martino, Giacomo Casella, Federico Colombo, Annamaria Finardi, Luca Muzio, Hélène Descamps, Antonello E. Spinelli, Roberto Furlan
Přispěvatelé: Casella, Giacomo, Colombo, Federico, Finardi, Annamaria, Descamps, Hélène, Ill-Raga, Gerard, Spinelli, Antonello, Podini, Paola, Bastoni, Mattia, Martino, Gianvito, Muzio, Luca, Furlan, Roberto
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Multiple Sclerosis
medicine.medical_treatment
Cell Line
neuroinflammation
03 medical and health sciences
Extracellular Vesicles
Mice
Downregulation and upregulation
Microscopy
Electron
Transmission
Genetic
Drug Discovery
Genetics
medicine
Animals
Molecular Biology
Neuroinflammation
Interleukin 4
Cells
Cultured
Lactadherin
Pharmacology
CD11b Antigen
Microglia
Chemistry
Reverse Transcriptase Polymerase Chain Reaction
Macrophages
Drug Discovery3003 Pharmaceutical Science
Experimental autoimmune encephalomyelitis
phagocyte
medicine.disease
Cell biology
Rats
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Cytokine
Microscopy
Fluorescence
Drug delivery
Molecular Medicine
Female
Original Article
Interleukin-4
extracellular vesicle
Popis: 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 107 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. Extracellular vesicles (EVs) are a physiological way of intercellular communication. We show here that it is possible to deliver EVs engineered to contain different molecules for therapeutic purposes. Using this strategy, we have successfully delivered an anti-inflammatory cytokine to treat a mouse model of multiple sclerosis.
Databáze: OpenAIRE
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