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Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages

AutorGuglielmetti, C.; Salas-Perdomo, Angélica ; Planas, Anna M. ; Ponsaerts, Peter
Palabras claveMagnetic resonance imaging
Multiple sclerosis
Demyelination
Fecha de publicacióndic-2016
EditorJohn Wiley & Sons
CitaciónGlia 64(12): 2181-2200 (2016)
ResumenDetrimental inflammatory responses in the central nervous system are a hallmark of various brain injuries and diseases. With this study we provide evidence that lentiviral vector-mediated expression of the immune-modulating cytokine interleukin 13 (IL-13) induces an alternative activation program in both microglia and macrophages conferring protection against severe oligodendrocyte loss and demyelination in the cuprizone mouse model for multiple sclerosis (MS). First, IL-13 mediated modulation of cuprizone induced lesions was monitored using T-weighted magnetic resonance imaging and magnetization transfer imaging, and further correlated with quantitative histological analyses for inflammatory cell influx, oligodendrocyte death, and demyelination. Second, following IL-13 immune gene therapy in cuprizone-treated eGFP bone marrow chimeric mice, we provide evidence that IL-13 directs the polarization of both brain-resident microglia and infiltrating macrophages towards an alternatively activated phenotype, thereby promoting the conversion of a pro-inflammatory environment toward an anti-inflammatory environment, as further evidenced by gene expression analyses. Finally, we show that IL-13 immune gene therapy is also able to limit lesion severity in a pre-existing inflammatory environment. In conclusion, these results highlight the potential of IL-13 to modulate microglia/macrophage responses and to improve disease outcome in a mouse model for MS. GLIA 2016;64:2181–2200.
Versión del editorhttps://doi.org/10.1002/glia.23053
URIhttp://hdl.handle.net/10261/148662
DOI10.1002/glia.23053
Identificadoresdoi: 10.1002/glia.23053
issn: 1098-1136
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