Abstract
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.
Keywords:
macrophage; miR-223; microRNA; microglia; multiple sclerosis; phagocytosis; polarization; remyelination.
© 2018 Wiley Periodicals, Inc.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Case-Control Studies
-
Cells, Cultured
-
Corpus Callosum / pathology
-
Demyelinating Autoimmune Diseases, CNS / etiology
-
Demyelinating Autoimmune Diseases, CNS / pathology*
-
Demyelinating Autoimmune Diseases, CNS / physiopathology*
-
Demyelinating Autoimmune Diseases, CNS / therapy
-
Disease Models, Animal
-
Freund's Adjuvant / toxicity
-
Glial Fibrillary Acidic Protein / genetics
-
Glial Fibrillary Acidic Protein / metabolism
-
Humans
-
Lipopolysaccharides / toxicity
-
Lysophosphatidylcholines / toxicity
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
MicroRNAs / genetics
-
MicroRNAs / metabolism*
-
Microglia / drug effects
-
Microglia / metabolism
-
Monocytes / drug effects
-
Monocytes / metabolism
-
Myelin-Oligodendrocyte Glycoprotein / toxicity
-
Myeloid Cells / metabolism
-
Myeloid Cells / physiology*
-
Peptide Fragments / toxicity
-
Phagocytosis / drug effects
-
Phagocytosis / physiology
-
Reactive Oxygen Species / metabolism
Substances
-
Glial Fibrillary Acidic Protein
-
Lipopolysaccharides
-
Lysophosphatidylcholines
-
MIRN223 microRNA, mouse
-
MicroRNAs
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
Reactive Oxygen Species
-
myelin oligodendrocyte glycoprotein (35-55)
-
Freund's Adjuvant