Interleukin-13 immune gene therapy prevents CNS inflammation and demyelination via alternative activation of microglia and macrophages: Modulation of CNS Inflammation by Interkeukin-13
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 T2-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
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Both T2 and MTR measures are highly correlated to brain microstructure and underlying histopathological events following cuprizone administration.
“Guglielmetti et al. reported that both T2 and MTR measures are highly correlated to the brain microstructure and underlying histopathological events following cuprizone administration (Guglielmetti et al. 2016a).”
From Neurite orientation dispersion and density imaging of mouse brain microstructure (2019) · cites this paper as Guglielmetti et al. 2016a
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- Authors
- Guglielmetti, C., Le Blon, D., Santermans, E., Salas-Perdomo, A., Daans, J., De Vocht, N., Shah, D., Hoornaert, C., Praet, J., Peerlings, J., Kara, F., Bigot, C., Mai, Z., Goossens, H., Hens, N., Hendrix, S., Verhoye, M., Planas, A. M., Berneman, Z., van der Linden, A., & Ponsaerts, P.
- Affiliations
- University of Antwerp (BE)
- Laboratory of Experimental Hematology, Faculty of Medicine and Health Sciences; University of Antwerp; Antwerp Belgium
- Hasselt University (BE)
- Department of Brain Ischemia and Neurodegeneration; Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Barcelona Spain
- Bio-Imaging Laboratory, Department of Biomedical Sciences; University of Antwerp; Antwerp Belgium
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Ponsaerts, Peter
- ORCID
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2016-09-29
- Volume
- 64
- Issue
- 12
- Pages
- 2181-2200
- ISSN
- 0894-1491 (ISSN-L)
- OpenAlex
- W2529854313
- Cited by
- 76
- References
- 101
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 14 · 2021: 6 · 2020: 15 · 2019: 13 · 2018: 4 · 2017: 9
- FWCI
- 7.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- Funders
- European Commission
- Fonds Wetenschappelijk Onderzoek
- Fondation Charcot
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- IL-13, gene therapy, microglia, macrophages, alternative activation, demyelination, oligodendrocyte loss, cuprizone, multiple sclerosis, neuroinflammation, lentiviral vectors, bone marrow chimeric mice, magnetization transfer imaging
- MeSH terms
- Animals, Antigens, Differentiation, Cuprizone, Demyelinating Diseases, Disease Models, Animal, Encephalitis, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Monoamine Oxidase Inhibitors, Myelin Proteins, Nerve Tissue Proteins, Transduction, Genetic, Genetic Therapy, Bone Marrow Transplantation, Cytokines, Microglia, Interleukin-13, Green Fluorescent Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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