Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/23036
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

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