miR‐155 as a multiple sclerosis–relevant regulator of myeloid cell polarization
Open accessAbstract
Objective: To define the functional significance of increased miR‐155 expression in myeloid cells in multiple sclerosis (MS). Methods: miR‐155 expression levels were measured in CD14 + monocytes from untreated relapsing–remitting MS patients and compared to healthy controls. Similar microRNA (miRNA) analyses were performed in laser‐captured CD68 + cells from perivascular (blood‐derived macrophages) and parenchymal (microglia) brain regions in both active MS lesions and noninflammatory cases. Using human adult blood‐derived macrophages and brain‐derived microglia, in vitro experiments were performed to demonstrate how miR‐155 influences the polarization state, phenotype, and functional properties of myeloid cells, in addition to their ability to subsequently impact adaptive T‐cell responses. Results: In MS, miR‐155 expression was significantly increased in both peripheral circulating CD14 + monocytes and active lesions (CD68 + cells) compared to control donor monocytes and parenchymal microglia, respectively. In vitro, miR‐155 was significantly increased in both M1‐polarized primary human macrophages and microglia. Transfection of an miR‐155 mimic increased proinflammatory cytokine secretion and costimulatory surface marker expression in both cell types; an miR‐155 inhibitor decreased proinflammatory cytokine expression. Coculture experiments demonstrated that allogeneic T‐cell responses were significantly enhanced in the presence of miR‐155–transfected myeloid cells compared to controls. Interpretation: Our results demonstrate that miR‐155 regulates proinflammatory responses in both blood‐derived and central nervous system (CNS)‐resident myeloid cells, in addition to impacting subsequent adaptive immune responses. Differential miRNA expression may therefore provide insight into mechanisms responsible for distinct phenotypic and functional properties of myeloid cells, thus impacting their ability to influence CNS injury and repair. Ann Neurol 2013;74:709–720
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Since many disorders share the same proteins or micro RNAs as markers, it is impossible to have selective detection of diseases.
“Also, since many disorders share the same proteins or micro RNAs as markers, it is impossible to have selective detection of diseases [313–317].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [314]
miR-155 is upregulated in M1-polarized macrophages and microglia, and in those cells in multiple sclerosis patients.
“MiR-155 is upregulated in M1-polarized macrophages and microglia, and in those cells in patients with multiple sclerosis [248].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [248]
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“An anti-miR towards miR-155 could also be a viable option for delivery to SCIs as the miRNA has been shown to promote M1 polarization in human macrophages while its inhibition blunts the expression of pro-inflammatory cytokines in a MS model.(56) It has recently been shown that miRNA let-7c promotes M2 polarization by…”
miR-155 in the progression of lung fibrosis in systemic sclerosis
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“Comprehensive characterization of the phenotype and functional properties of our polarized human macrophages and microglia was performed previously (11, 12, 19).”
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“…in inflammatory CNS disorders, including human ex vivo specimens and animal models of amyotrophic lateral sclerosis (ALS) (Koval et al., 2013), multiple sclerosis (MS) (Junker, 2011; Murugaiyan et al., 2011; Moore et al., 2013), and Down syndrome (Keck-Wherley et al., 2011; Wang et al., 2013).”
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“miR-155 promotes proinflammatory responses in microglia and astrocytes by targeting SOCS1 [76, 77].”
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“Several studies have documented abnormal miRNA profiles in peripheral blood immune cells as well as CNS glial cells of patients with MS, compared to controls [13,14], raising the possibility that such altered miRNA expression might be responsible for immunological features associated with MS pathogenesis.”
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“In the CNS, miR-155-5p is implicated in the onset or progression of amyotrophic lateral sclerosis (Koval et al., 2013) and multiple sclerosis (O’Connell et al., 2010; Murugaiyan et al., 2011; Moore et al., 2013).”
BackgroundInfluentialmiR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review
Maciak, K., Dziedzic, A., Miller, E. D., & Saluk, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094332 · Cited by 87 · see citing works
“Available data identify miR-155 as so-called inflamma-miR, a powerful activator of the inflammation, the essential miR in the autoimmune diseases’ pathogenesis because of its influence on myeloid cell polarization to a phenotypic and functional pro-inflammatory form [12,13].”
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“MS SOCS1 ↑ Blood monocytes, myeloid cells from brain lesion in RRMS patients [131]”
BackgroundRoles of CircRNAs in Autoimmune Diseases
Xia, X., Tang, X., & Wang, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00639 · Cited by 83 · see citing works
“ANXA2 is reported to be a target of miR-155, whose expression increases greatly in PBMCs and correlates with disease severity in MS patients (63).”
BackgroundMicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis
Morquette, B., Juźwik, C. A., Drake, S., Charabati, M., Zhang, Y., Lécuyer, M., Galloway, D. A., Dumas, A., de Faria, O., Paradis-Isler, N., et al. (2019) · Brain · doi:10.1093/brain/awz245 · Cited by 84 · see citing works
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“microglia and promotes a pro-inflammatory phenotype [5, 36].”
MicroRNA-155 Implication in M1 Polarization and the Impact in Inflammatory Diseases
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“To date, several miRs, such as miR‐7, miR‐124, miR‐153, and miR‐155, were showed treatment effect in PD via inhibition of neuroinflammation (Doxakis, 2010; Moore et al., 2013).”
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Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis
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Effects of fumarates on circulating and CNS myeloid cells in multiple sclerosis
Michell‐Robinson, M. A., Moore, C. S., Healy, L. M., Osso, L. A., Garbajs, N. Z., Grouza, V., Touil, H., Poliquin‐Lasnier, L., Trudelle, A., Giacomini, P. S., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.270 · Cited by 74 · see citing works
“As a marker of myeloid cell inflammatory activity, we chose micro-RNA 155 (miR-155), an established inducer of proinflammatory cytokine secretion, previously shown to have increased expression in myeloid cells from MS patients.(21) We present data demonstrating in vivo effects of DMF therapy on these responses in mono…”
ResultSelf-citationNoncoding RNAs in multiple sclerosis
Yang, X., Wu, Y., Zhang, B., & Ni, B. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0586-9 · Cited by 73 · see citing works
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“In addition, the Overexpression of miR-155 was found in various cells of the immune and nervous system, including myeloid-derived macrophages, microglia, T and B cells, and astrocytes, besides resident brain cells (73, 75).”
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Dysregulation of Inflammasome Priming and Activation by MicroRNAs in Human Immune-Mediated Diseases
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“miR-7-5p MS CD4 T cells Up t versus ut (96) miR-9-5p MS Leukocytes Up MS versus hs (91) RA Plasma Down RA versus hs (99) miR-17-5p MS CD4 T cells Up rl versus rm (95) MS CD4 T cells Down t versus ut (95) SLE PBMC Down SLE versus hs (114, 115) SLE PBMC Up t versus ut (116) miR-20a-5p SLE Monocytes Down SLE versus hs (1…”
Regulation of Macrophage, Dendritic Cell, and Microglial Phenotype and Function by the SOCS Proteins
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“More importantly, systemic delivery of antisense peptide nucleic acids has been effective in rodent models of MS (193, 198, 199), Alzheimer’s disease (200, 201), ALS (202), and ischemic stroke (202).”
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Epigenetic Modifications and Therapy in Multiple Sclerosis
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“…miRNAs (Fenoglio et al. 2012; Huynh and Casaccia 2013; Junker et al. 2011; Thamilarasan et al. 2012; Otaegui et al. 2009; Junker et al. 2009; Moore et al. 2013; Guerau-de-Arellano et al. 2011; Noorbakhsh et al. 2011; Du et al. 2009; Siegel et al. 2012; Fenoglio et al. 2013; Søndergaard et…”
BackgroundResultInfluentialMicroRNA in multiple sclerosis
Gao, Y., Han, D. K., & Feng, J. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.01.020 · Cited by 67 · see citing works
MicroRNAs associated with the pathogenesis of multiple sclerosis
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Dysregulated Network of miRNAs Involved in the Pathogenesis of Multiple Sclerosis
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Galloway, D. A., Blandford, S. N., Berry, T., Williams, J. B., Stefanelli, M., Ploughman, M., & Moore, C. S. (2019) · Glia · doi:10.1002/glia.23576 · Cited by 64 · see citing works
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“Meanwhile, the expression of miR-155 in patients with multiple sclerosis increased in peripheral and CNSresident myeloid cells, such as circulating monocytes and activated microglia [19].”
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“Different types of miRNAs are regulated in blood and brain lesions of multiple sclerosis (MS) patients [27,28].”
BackgroundCirculating Inflammatory miRNAs Associated with Parkinson’s Disease Pathophysiology
Oliveira, S. R., Dionísio, P. A., Guedes, L. C., Gonçalves, N., Coelho, M. M., Rosa, M. M., Amaral, J. D., Ferreira, J. J., & Rodrigues, C. M. P. (2020) · Biomolecules · doi:10.3390/biom10060945 · Cited by 59 · see citing works
“In the past few years, miRNA deregulation has been implicated in several neurodegenerative diseases, such as Alzheimer’s disease [9,10], amyotrophic lateral sclerosis [11,12], multiple sclerosis [13,14], and PD [15–17], where it contributes to neurodegeneration and disease progression.”
miRNAs As Emerging Regulators of Oligodendrocyte Development and Differentiation
Galloway, D. A., & Moore, C. S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00059 · Cited by 59 · see citing works
“…to inflammation and immune cell activity, potential Frontiers in Cell and Developmental Biology | www.frontiersin.org 5 June 2016 | Volume 4 | Article 59 miRNA biomarkers have been assessed in the peripheral compartment and include the miR-145 and -155 (Keller et al., 2009; Moore et al., 2013).”
BackgroundSelf-citationDickey, L. L., Worne, C. L., Glover, J. L., Lane, T. E., & O’Connell, R. M. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0699-z · Cited by 58 · see citing works
“sion include regulation of proinflammatory responses in blood-derived and CNS-resident myeloid cells [91].”
BackgroundMa, S., Fan, L., Li, J., Zhang, B., & Yan, Z. (2019) · International Journal of Neuroscience · doi:10.1080/00207454.2019.1707817 · Cited by 57 · see citing works
“Excitingly, the inhibition of miR-155 has been verified to be beneficial for some neuro-immune diseases [12,13].”
BackgroundRegulation of brain endothelial barrier function by microRNAs in health and neuroinflammation
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miR-155 Dysregulation and Therapeutic Intervention in Multiple Sclerosis
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miR-330-5p/Tim-3 axis regulates macrophage M2 polarization and insulin resistance in diabetes mice
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The potential role of miRNA in regulating macrophage polarization
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Meta-Analysis of Differential miRNA Expression after Bariatric Surgery
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Heterogeneity of oligodendrocyte progenitor cells in adult human brain
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Self-citationQuaking andmiR-155interactions in inflammation and leukemogenesis
Tili, E., Chiabai, M. A., Palmieri, D., Brown, M., Cui, R., Fernandes, C., Richmond, T. K., Kim, T., Sheetz, T. J., Sun, H., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5248 · Cited by 50 · see citing works
“As miR-155 expression is elevated in neuro-inflammatory pathologies such as MS or ALS [41, 42], our data further suggest that a lack of QKI anti-inflammatory input may result in the deleterious dominance of miR-155 activity, therefore, miR-155-QKI interactions could prove to be significantly important for future thera…”
Effects of fumarates on inflammatory human astrocyte responses and oligodendrocyte differentiation
Galloway, D. A., Williams, J. B., & Moore, C. S. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.414 · Cited by 50 · see citing works
“miR-146a is an inflammation resolving microRNA whose expression is upregulated in CNS lesions and peripheral immune cells of MS patients.(35,36) As such, the reduced expression of miR-146a in fumarate-treated astrocytes suggests an MS-relevant resolution of inflammation.”
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Is It worth Considering Circulating microRNAs in Multiple Sclerosis?
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“miR-155 upregulation in microglia promotes its activation, which is detected in part through proinflammatory cytokine secretion (28).”
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Let-7f-5p suppresses Th17 differentiation via targeting STAT3 in multiple sclerosis
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Glial Cells as Regulators of Neuroimmune Interactions in the Central Nervous System
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“This finding contrasts to its upregulation in fetal human astrocytes exposed in vitro to IL-1b/IFN-g and its upregulation in myeloid cells microdissected from acute inflammatory lesions (70, 71).”
ResultSelf-citationRole and Dysregulation of miRNA in Patients with Parkinson’s Disease
Salemi, M., Marchese, G., Lanza, G., Cosentino, F., Salluzzo, M. G., Schillaci, F. A., Ventola, G. M., Cordella, A., Ravo, M., & Ferri, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010712 · Cited by 47 · see citing works
“Evidence in the literature suggests that miRNA deregulation has been implicated in several neurodegenerative diseases, such as Alzheimer’s disease (AD) [14–16], amyotrophic lateral sclerosis (ALS) [17,18], multiple sclerosis (MS) [19], and PD [20].”
BackgroundMultiple Sclerosis: Roles of miRNA, lcnRNA, and circRNA and Their Implications in Cellular Pathways
Cipriano, G. L., Schepici, G., Mazzon, E., & Anchesi, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042255 · Cited by 45 · see citing works
“…the dysregulated immune response characteristic of MS patients, while upregulated miR-155 was found in peripheral circulating monocytes of RRMS patients. which was found to induce the M1polarization state of human macrophages and microglia, thereby forcing pro-inflammatory responses [54,55].”
- Authors
- Moore, C. S., Rao, V. T. S., Durafourt, B. A., Bedell, B. J., Ludwin, S. K., Bar‐Or, A., & Antel, J. P.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Queen's University (CA)
- Corresponding author
- Moore, Craig S.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-09-23
- Volume
- 74
- Issue
- 5
- Pages
- 709-720
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W1915908724
- Cited by
- 219
- References
- 48
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 13 · 2021: 15 · 2020: 25 · 2019: 26 · 2018: 23 · 2017: 24 · 2016: 23 · 2015: 15 · 2014: 15 · 2013: 2
- FWCI
- 13.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- miR-155, multiple sclerosis, myeloid cell polarization, microglia, blood-derived macrophages, CD14+ monocytes, M1 macrophage polarization, inflammatory cytokines, costimulatory molecules, T cell response, relapsing-remitting multiple sclerosis, neuroinflammation
- MeSH terms
- Adult, Aged, Brain, Female, Humans, Macrophages, Male, Middle Aged, Multiple Sclerosis, T-Lymphocytes, Cell Polarity, Microglia, Myeloid Cells, MicroRNAs, Cell Proliferation, Adaptive Immunity
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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