Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis
| Autor: | Stephan A. Müller, Maria Inês Cunha, Stefan F. Lichtenthaler, Anne Winkler, Bettina Schmid, Franziska van der Meer, Tjakko J. van Ham, Ioannis Alexopoulos, Mikael Simons, Minhui Su, Minou Djannatian, Christine Stadelmann, Martina Schifferer, Ludovico Cantuti-Castelvetri |
|---|---|
| Přispěvatelé: | Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proteome metabolism [Myelin Sheath] drug effects [Oligodendroglia] metabolism [Microglia] metabolism [Lysophosphatidylcholines] drug effects [Microglia] pathology [Phagocytes] Myelin Mice 0302 clinical medicine Phagosomes Immunology and Allergy Macrophage drug effects [Axons] Zebrafish Cells Cultured Myelin Sheath Phagocytes pathology [Axons] drug effects [Phagocytes] Microglia biology Chemistry pharmacology [Tumor Necrosis Factor-alpha] metabolism [Myeloid Differentiation Factor 88] 3. Good health Cell biology Oligodendroglia medicine.anatomical_structure Spinal Cord Larva drug effects [Myelin Sheath] Immunology genetics [Mutation] pathology [Spinal Cord] Article metabolism [Oligodendroglia] 03 medical and health sciences Inflammation resolution drug effects [Phagosomes] pathology [Myelin Sheath] medicine Animals ddc:610 drug effects [Remyelination] Remyelination pathology [Inflammation] Inflammation Innate immune system Tumor Necrosis Factor-alpha Macrophages drug effects [Larva] Lysophosphatidylcholines metabolism [Proteome] biology.organism_classification Spinal cord Axons Disease Models Animal 030104 developmental biology pathology [Oligodendroglia] Mutation Myeloid Differentiation Factor 88 metabolism [Phagosomes] pathology [Demyelinating Diseases] 030217 neurology & neurosurgery Neuroscience Demyelinating Diseases |
| Zdroj: | Journal of Experimental Medicine, 217(5):e20191390. Rockefeller University Press The Journal of Experimental Medicine Journal of experimental medicine 217(5), e20191390 (2020). doi:10.1084/jem.20191390 Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| DOI: | 10.1084/jem.20191390 |
| Popis: | We find that pro-inflammatory activation is required for remyelination after myelin injury. We impaired inflammatory signaling and found that microglia in lesioned animals were defective in phagosome maturation, debris clearance, and also in triggering the generation of new oligodendrocytes, a process which required TNF-α. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|