miR‐223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system
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.
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miR-223 knockout in experimental autoimmune encephalomyelitis mice delays disease onset without affecting severity.
“Its knock-out in experimental autoimmune encephalomyelitis mice led to delayed onset of the disease, but without affecting its severity.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [240]
Absence of miR-223 impairs M2 polarization and phagocytosis, reducing myelin debris clearance in vivo.
“However, absence of the miR-223 impairs M2 polarization and phagocytosis, which results in vivo in reduced myelin debris clearance [240].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [240]
miR-223 is associated with the M2 phenotype.
“MiR-223 is associated with the M2 phenotype.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [240]
Cites
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“This is important as both microRNAs (Rupaimoole & Slack, 2017) and remyelination-targeting therapeutics (Plemel, Liu, & Yong, 2017) are translated to clinical populations.”
BackgroundIdentification of a unique TGF-β–dependent molecular and functional signature in microglia
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“Although this may suggest that miR-223 expression is detrimental in MS, the EAE model does not fully reflect the pathological features of MS and is an inefficient model to study repair and remyelination (Franklin & Ffrench-Constant, 2017).”
BackgroundMacrophages in inflammatory multiple sclerosis lesions have an intermediate activation status
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miR-223: An Effective Regulator of Immune Cell Differentiation and Inflammation
Jiao, P., Wang, X.-P., Luoreng, Z.-M., Yang, J., Jia, L., Ma, Y., & Wei, D.-W. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.59876 · Cited by 151 · see citing works
Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes
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Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis
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MicroRNAs as Regulators of Phagocytosis
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- Authors
- Galloway, D. A., Blandford, S. N., Berry, T., Williams, J. B., Stefanelli, M., Ploughman, M., & Moore, C. S.
- Affiliations
- Memorial University of Newfoundland (CA)
- Corresponding author
- Moore, Craig S.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2018-12-11
- Volume
- 67
- Issue
- 5
- Pages
- 857-869
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2905045032
- Cited by
- 64
- References
- 8
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 13 · 2023: 5 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 3
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society of Canada (EGID2735)
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-223, myeloid cells, macrophages, microglia, multiple sclerosis, demyelination, remyelination, M2 macrophage polarization, neuroinflammation, phagocytosis, myelin debris clearance, microRNA, neurodegenerative diseases, central nervous system repair
- MeSH terms
- Animals, Cells, Cultured, Corpus Callosum, Disease Models, Animal, Freund's Adjuvant, Glial Fibrillary Acidic Protein, Humans, Lipopolysaccharides, Lysophosphatidylcholines, Male, Mice, Inbred C57BL, Monocytes, Peptide Fragments, Phagocytosis, Case-Control Studies, Reactive Oxygen Species, Microglia, Mice, Knockout, Demyelinating Autoimmune Diseases, CNS, Myeloid Cells, MicroRNAs, Mice, Myelin-Oligodendrocyte Glycoprotein
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