Journal
JOURNAL OF NEUROSCIENCE
Volume 35, Issue 1, Pages 4-20Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0849-14.2015
Keywords
cytokines; migration; multiple sclerosis; Oligodendrocyte progenitor cells; remyelination
Categories
Funding
- Fondation ARSEP
- UK Multiple Sclerosis Society
- French National Agency for Research
- French Medical Research Foundation
- program Investissements d'avenir [ANR-10-IAIHU-06]
- Rosetrees Trust [M144] Funding Source: researchfish
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The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult CNS, to obtain a comprehensive picture of how they become activated after demyelination and how this enables them to contribute to remyelination. We find that adult OPCs have a transcriptome more similar to that of oligodendrocytes than to neonatal OPCs, but revert to a neonatal-like transcriptome when activated. Part of the activation response involves increased expression of two genes of the innate immune system, IL1 beta and CCL2, which enhance the mobilization of OPCs. Our results add a new dimension to the role of the innate immune system in CNS regeneration, revealing how OPCs themselves contribute to the postinjury inflammatory milieu by producing cytokines that directly enhance their repopulation of areas of demyelination and hence their ability to contribute to remyelination.
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