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miR‐223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system
Author(s) -
Galloway Dylan A.,
Blandford Stephanie N.,
Berry Tangyne,
Williams John B.,
Stefanelli Mark,
Ploughman Michelle,
Moore Craig S.
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23576
Subject(s) - remyelination , neuroinflammation , microglia , biology , multiple sclerosis , central nervous system , neuroscience , myelin , phenotype , immunology , microbiology and biotechnology , myeloid , inflammation , gene , biochemistry
In the injured central nervous system, myeloid cells, including macrophages and microglia, are key contributors to both myelin injury and repair. This immense plasticity emphasizes the need to further understand the precise molecular mechanisms that contribute to the dynamic regulation of myeloid cell polarization and function. Herein, we demonstrate that miR‐223 is upregulated in multiple sclerosis (MS) patient monocytes and the alternatively‐activated and tissue‐regenerating M2‐polarized human macrophages and microglia. Using miR‐223 knock‐out mice , we observed that miR‐223 is dispensable for maximal pro‐inflammatory responses, but is required for efficient M2‐associated phenotype and function, including phagocytosis. Using the lysolecithin animal model, we further demonstrate that miR‐223 is required to efficiently clear myelin debris and promote remyelination. These results suggest miR‐223 constrains neuroinflammation while also promoting repair, a finding of important pathophysiological relevance to MS as well as other neurodegenerative diseases.