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Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2020 May 04; Vol. 217 (5). - Publication Year :
- 2020
-
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.<br />Competing Interests: Disclosures: The authors declare no competing interests exist.<br /> (© 2020 Cunha et al.)
- Subjects :
- Animals
Axons drug effects
Axons pathology
Cells, Cultured
Disease Models, Animal
Larva drug effects
Lysophosphatidylcholines metabolism
Mice
Microglia drug effects
Microglia metabolism
Mutation genetics
Myelin Sheath drug effects
Myelin Sheath pathology
Myeloid Differentiation Factor 88 metabolism
Oligodendroglia drug effects
Oligodendroglia metabolism
Phagocytes drug effects
Phagocytes pathology
Phagosomes drug effects
Phagosomes metabolism
Proteome metabolism
Remyelination drug effects
Spinal Cord pathology
Tumor Necrosis Factor-alpha pharmacology
Zebrafish
Demyelinating Diseases pathology
Inflammation pathology
Myelin Sheath metabolism
Oligodendroglia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 217
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32078678
- Full Text :
- https://doi.org/10.1084/jem.20191390