MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47
Abstract
We established microRNA profiles from active and inactive multiple sclerosis lesions. Using laser capture microdissection from multiple sclerosis lesions to pool single cells and in vitro cultures, we assigned differentially expressed microRNA to specific cell types. Astrocytes contained all 10 microRNA that were most strongly upregulated in active multiple sclerosis lesions, including microRNA-155, which is known to modulate immune responses in different ways but so far had not been assigned to central nervous system resident cells. MicroRNA-155 was expressed in human astrocytes in situ, and further induced with cytokines in human astrocytes in vitro. This was confirmed with astrocyte cultures from microRNA-155-|-lacZ mice. We matched microRNA upregulated in phagocytically active multiple sclerosis lesions with downregulated protein coding transcripts. This converged on CD47, which functions as a 'don't eat me' signal inhibiting macrophage activity. Three microRNA upregulated in active multiple sclerosis lesions (microRNA-34a, microRNA-155 and microRNA-326) targeted the 3'-untranslated region of CD47 in reporter assays, with microRNA-155 even at two distinct sites. Our findings suggest that microRNA dysregulated in multiple sclerosis lesions reduce CD47 in brain resident cells, releasing macrophages from inhibitory control, thereby promoting phagocytosis of myelin. This mechanism may have broad implications for microRNA-regulated macrophage activation in inflammatory diseases.
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miR-155 is upregulated in astrocytes from active multiple sclerosis lesions, along with miR-34a and miR-326, contributing to reduced CD47 expression.
“It is also upregulated in astrocytes from active multiple sclerosis lesions (along with miR-34a and miR-326), contributing to reduced expression of CD47.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [249]
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- Authors
- Junker, A., Krumbholz, M., Eisele, S., Mohan, H., Augstein, F., Bittner, R., Lassmann, H., Wekerle, H., Hohlfeld, R., & Meinl, E.
- Affiliations
- Max Planck Institute of Neurobiology (DE)
- Medical University of Vienna (AT)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12
- Volume
- 132
- Issue
- 12
- Pages
- 3342-3352
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2143890525
- Cited by
- 595
- References
- 7
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 29 · 2023: 29 · 2022: 31 · 2021: 54 · 2020: 45 · 2019: 32 · 2018: 40 · 2017: 41 · 2016: 42 · 2015: 48 · 2014: 38 · 2013: 56 · 2012: 35
- FWCI
- 17.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Hermann und Lilly Schilling-Stiftung für Medizinische Forschung
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, miRNA expression profiling, CD47, miR-155, miR-34a, astrocytes, macrophage activation, 3'-untranslated region targeting, cytokine induction, neuroinflammation
- MeSH terms
- Adult, Animals, Astrocytes, Brain, Cells, Cultured, Female, Humans, Macrophages, Male, Middle Aged, Multiple Sclerosis, Myelin Sheath, Phagocytosis, Autoimmunity, Polymerase Chain Reaction, Mice, Knockout, Gene Expression Profiling, MicroRNAs, Microdissection, Mice, CD47 Antigen
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