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Title: | Interleukin-13 Immune Gene Therapy Prevents CNS Inflammation and Demyelination via Alternative Activation of Microglia and Macrophages | Authors: | Guglielmetti, Caroline Le Blon, Debbie SANTERMANS, Eva Salas-Perdomo, Angelica Daans, Jasmijn De Vocht, Nathalie Shah, Disha Hoornaert, Chloe Praet, Jelle Peerlings, Jurgen Kara, Firat Bigot, Christian Mai, Zhenhua Goossens, Herman HENS, Niel HENDRIX, Sven Verhoye, Marleen Planas, Anna M. Berneman, Zwi van der Linden, Annemie Ponsaerts, Peter |
Issue Date: | 2016 | Publisher: | WILEY-BLACKWELL | Source: | GLIA, 64(12), p. 2181-2200 | Abstract: | Detrimental 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-2-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. | Notes: | [Guglielmetti, Caroline; De Vocht, Nathalie; Shah, Disha; Praet, Jelle; Peerlings, Jurgen; Kara, Firat; Bigot, Christian; Mai, Zhenhua; Verhoye, Marleen; van der Linden, Annemie] Univ Antwerp, Dept Biomed Sci, Bioimaging Lab, Antwerp, Belgium. [Le Blon, Debbie; Daans, Jasmijn; De Vocht, Nathalie; Hoornaert, Chloe; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Fac Med & Hlth Sci, Lab Expt Hematol, Antwerp, Belgium. [Le Blon, Debbie; Daans, Jasmijn; De Vocht, Nathalie; Hoornaert, Chloe; Goossens, Herman; Hens, Niel; Berneman, Zwi; Ponsaerts, Peter] Univ Antwerp, Vaccine & Infect Dis Inst Vaxinfectio, Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, I Biostat, Ctr Stat, Hasselt, Belgium. [Salas-Perdomo, Angelica; Planas, Anna M.] IDIBAPS, CSIC, IIBB, Dept Brain Ischemia & Neurodegenerat, Barcelona, Spain. [Mai, Zhenhua] Icometrix, Leuven, Belgium. [Hens, Niel] Univ Antwerp, Ctr Hlth Econ Res & Modelling Infect Dis Chermid, Antwerp, Belgium. [Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Dept Morphol, Diepenbeek, Belgium. | Keywords: | demyelination; multiple sclerosis; magnetic resonance imaging;demyelination; multiple sclerosis; magnetic resonance imaging | Document URI: | http://hdl.handle.net/1942/23036 | ISSN: | 0894-1491 | e-ISSN: | 1098-1136 | DOI: | 10.1002/glia.23053 | ISI #: | 000386751100010 | Rights: | (C) 2016 Wiley Periodicals, Inc. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2017 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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guglielmetti 1.pdf Restricted Access | Published version | 1.84 MB | Adobe PDF | View/Open Request a copy |
Guglielmetti et al. - accepted manuscript.pdf | Peer-reviewed author version | 6.55 MB | Adobe PDF | View/Open |
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