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dc.contributor.authorGuglielmetti, Caroline-
dc.contributor.authorLe Blon, Debbie-
dc.contributor.authorSANTERMANS, Eva-
dc.contributor.authorSalas-Perdomo, Angelica-
dc.contributor.authorDaans, Jasmijn-
dc.contributor.authorDe Vocht, Nathalie-
dc.contributor.authorShah, Disha-
dc.contributor.authorHoornaert, Chloe-
dc.contributor.authorPraet, Jelle-
dc.contributor.authorPeerlings, Jurgen-
dc.contributor.authorKara, Firat-
dc.contributor.authorBigot, Christian-
dc.contributor.authorMai, Zhenhua-
dc.contributor.authorGoossens, Herman-
dc.contributor.authorHENS, Niel-
dc.contributor.authorHENDRIX, Sven-
dc.contributor.authorVerhoye, Marleen-
dc.contributor.authorPlanas, Anna M.-
dc.contributor.authorBerneman, Zwi-
dc.contributor.authorvan der Linden, Annemie-
dc.contributor.authorPonsaerts, Peter-
dc.identifier.citationGLIA, 64(12), p. 2181-2200-
dc.description.abstractDetrimental 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.-
dc.description.sponsorshipThis work was supported by research grants G.0136.11 (granted to PP, AVDL and ZB), G.0130.11 (granted to PP, AVDL and ZB) and G.0834.11 (granted to PP and SH) of the Fund for Scientific Research-Flanders (FWO-Vlaanderen, Belgium), in part by a Methusalem research grant from the Flemish government (granted to HG), in part by funding received from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement 278850 (INMiND) (granted to AVdL and AMP), in part by the Brainpath project (MSCA IAPP project granted to AVdL) and in part by funding received from the Belgian Charcot Foundation (granted to PP and AVdL). DLB, DS and CG hold a PhD-studentship from the Flemish Institute for Science and Technology (IWT-Vlaanderen). NDV and CH hold a PhD-studentship from the FWO-Vlaanderen. FK and JP hold a post-doctoral fellowship from the FWO-Vlaanderen.-
dc.rights(C) 2016 Wiley Periodicals, Inc.-
dc.subject.otherdemyelination; multiple sclerosis; magnetic resonance imaging-
dc.subject.otherdemyelination; multiple sclerosis; magnetic resonance imaging-
dc.titleInterleukin-13 Immune Gene Therapy Prevents CNS Inflammation and Demyelination via Alternative Activation of Microglia and Macrophages-
dc.typeJournal Contribution-
dc.description.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.-
item.fulltextWith Fulltext-
item.fullcitationGuglielmetti, 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 (2016) Interleukin-13 Immune Gene Therapy Prevents CNS Inflammation and Demyelination via Alternative Activation of Microglia and Macrophages. In: GLIA, 64(12), p. 2181-2200.-
item.accessRightsOpen Access-
item.contributorSANTERMANS, Eva-
item.contributorLe Blon, Debbie-
item.contributorShah, Disha-
item.contributorGoossens, Herman-
item.contributorBigot, Christian-
item.contributorGuglielmetti, Caroline-
item.contributorvan der Linden, Annemie-
item.contributorKara, Firat-
item.contributorDaans, Jasmijn-
item.contributorHENS, Niel-
item.contributorVerhoye, Marleen-
item.contributorPeerlings, Jurgen-
item.contributorPlanas, Anna M.-
item.contributorDe Vocht, Nathalie-
item.contributorPraet, Jelle-
item.contributorMai, Zhenhua-
item.contributorPonsaerts, Peter-
item.contributorSalas-Perdomo, Angelica-
item.contributorHoornaert, Chloe-
item.contributorHENDRIX, Sven-
item.contributorBerneman, Zwi-
item.validationecoom 2017-
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