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Cited by 160Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanisms

Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis

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Cunha, Maria Inês, Su, Minhui, Cantuti-Castelvetri, Ludovico, Müller, Stephan A., Schifferer, Martina, Djannatian, Minou, Alexopoulos, Ioannis, van der Meer, Franziska +6 more·2020·Journal of Experimental Medicine
DOI 10.1084/jem.20191390PMC PMC7201919
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Abstract

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB–dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-α in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

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  • The differentiation of local oligodendrocyte progenitor cells into actively myelinating oligodendrocytes is stimulated by innate immune cells.

    “Recent data have indicated that the differentiation of local oligodendrocyte progenitor cells into actively myelinating oligodendrocytes is stimulated by innate immune cells.64-67”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [66]

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Authors
Cunha, M. I., Su, M., Cantuti-Castelvetri, L., Müller, S. A., Schifferer, M., Djannatian, M., Alexopoulos, I., van der Meer, F., Winkler, A., van Ham, T. J., Schmid, B., Lichtenthaler, S. F., Stadelmann, C., & Simons, M.
Affiliations
  • Universidade do Porto (PT)
  • German Center for Neurodegenerative Diseases (DE)
  • Institute of Neuronal Cell Biology, Technical University Munich, Munich, Germany 1
  • Department of Neuropathology, University of Göttingen Medical Center, Göttingen, Germany 4
  • Universitätsmedizin Göttingen (DE)
  • Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands 5
Corresponding author
Simons, Mikael
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2020-02-20
Volume
217
Issue
5
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20191390
PMC
PMC7201919
OpenAlex
W3007536995
Cited by
160
References
16
Citations by year
2026: 18 · 2025: 28 · 2024: 38 · 2023: 22 · 2022: 23 · 2021: 19 · 2020: 12
FWCI
12.49
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-sa)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • DZNE Pub (submittedVersion, cc-by-nc-sa)
Funders
  • National Multiple Sclerosis Society
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Multiple Sclerosis Society
  • Deutsche Forschungsgemeinschaft (EXC 2145, TRR-274, 390857198, TRR128, STA 1389/2-1)
  • Technische Universität München
  • Deutschen Multiple Sklerose Gesellschaft
  • Zentrum für Regenerative Therapien Dresden
  • Fundação para a Ciência e a Tecnologia (PD/BD/105749/2014)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
remyelination, demyelination, myelin debris clearance, microglia, macrophages, pro-inflammatory activation, MyD88, NF-κB signaling, TNF-α, oligodendrogenesis, phagocytosis, spinal cord injury, zebrafish model, inflammation resolution
MeSH terms
Remyelination, Animals, Axons, Cells, Cultured, Demyelinating Diseases, Disease Models, Animal, Inflammation, Larva, Lysophosphatidylcholines, Mutation, Myelin Sheath, Oligodendroglia, Phagocytes, Phagosomes, Spinal Cord, Tumor Necrosis Factor-alpha, Zebrafish, Microglia, Proteome, Mice, Myeloid Differentiation Factor 88

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