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M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.

TitleM2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.
Publication TypeJournal Article
Year of Publication2013
AuthorsMiron VE, Boyd A, Zhao J-W, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams AC, Franklin RJM, ffrench-Constant C
JournalNat Neurosci
Date Published2013 Sep
KeywordsAdult, Aged, Aged, 80 and over, Animals, Animals, Newborn, Cadmium Chloride, Cell Differentiation, Cells, Cultured, Central Nervous System, Clodronic Acid, Culture Media, Conditioned, Demyelinating Diseases, Female, Humans, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia, Middle Aged, Myelin Proteins, Oligodendroglia, Rats, Rats, Sprague-Dawley, Regeneration

The lack of therapies for progressive multiple sclerosis highlights the need to understand the regenerative process of remyelination that can follow CNS demyelination. This involves an innate immune response consisting of microglia and macrophages, which can be polarized to distinct functional phenotypes: pro-inflammatory (M1) and anti-inflammatory or immunoregulatory (M2). We found that a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started. Oligodendrocyte differentiation was enhanced in vitro with M2 cell conditioned media and impaired in vivo following intra-lesional M2 cell depletion. M2 cell densities were increased in lesions of aged mice in which remyelination was enhanced by parabiotic coupling to a younger mouse and in multiple sclerosis lesions that normally show remyelination. Blocking M2 cell-derived activin-A inhibited oligodendrocyte differentiation during remyelination in cerebellar slice cultures. Thus, our results indicate that M2 cell polarization is essential for efficient remyelination and identify activin-A as a therapeutic target for CNS regeneration.

Alternate JournalNat. Neurosci.
PubMed ID23872599
PubMed Central IDPMC3977045
Grant List079249 / / Wellcome Trust / United Kingdom
089000 / / Wellcome Trust / United Kingdom
G0802545 / / Medical Research Council / United Kingdom
/ / Howard Hughes Medical Institute / United States
/ / Wellcome Trust / United Kingdom