Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

MicroRNAs and their Implications in CD4+ T-cells, Oligodendrocytes and Dendritic Cells in Multiple Sclerosis Pathogenesis

Author(s): Armin Safari*, Soheil Madadi*, Heidi Schwarzenbach, Mohsen Soleimani, Armita Safari, Mohammad Ahmadi and Meysam Soleimani*

Volume 23, Issue 7, 2023

Published on: 20 August, 2022

Page: [630 - 647] Pages: 18

DOI: 10.2174/1566524022666220525150259

Price: $65

Open Access Journals Promotions 2
Abstract

MicroRNAs (miRNAs) have been established as key players in various biological processes regulating differentiation, proliferation, inflammation, and autoimmune disorders. Emerging evidence suggests the critical role of miRNAs in the pathogenesis of multiple sclerosis (MS). Here, we provide a comprehensive overview of miRNAs, which are differentially expressed in MS patients or experimental autoimmune encephalomyelitis (EAE) mice and contribute to MS pathogenesis through regulating diverse pathways, including CD4+ T cells proliferation, differentiation, and activation in three subtypes of CD4+ T cells, including Th1, Th17 and regulatory T cells (Tregs). Moreover, the regulation of oligodendrocyte precursor cells (OPC) differentiation as a crucial player in MS pathogenesis is also described. Our literature research showed that miR-223 could affect different pathways involved in MS pathogenesis, such as promoting Th1 differentiation, activating the M2 phenotype of myeloid cells, and clearing myelin debris. MiR-223 was also identified as a potential biomarker, distinguishing relapsing-remitting multiple sclerosis (RRMS) from progressive multiple sclerosis (PMS), and thus, it may serve as an attractive target for further investigations. Our overview provides novel potential therapeutic targets for the treatment and new insights into miRNAs' role in MS pathogenesis.

Keywords: Oligodendrocytes, Th1 cells, T-regulatory cells, Th17 cells, dendritic cells, microRNAs.

[1]
Angelou CC, Wells AC, Vijayaraghavan J, et al. Differentiation of pathogenic th17 cells is negatively regulated by let-7 micrornas in a mouse model of multiple sclerosis. Front Immunol 2020; 10: 3125.
[http://dx.doi.org/10.3389/fimmu.2019.03125] [PMID: 32010153]
[2]
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15(9): 545-58.
[http://dx.doi.org/10.1038/nri3871] [PMID: 26250739]
[3]
Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med 2018; 378(2): 169-80.
[http://dx.doi.org/10.1056/NEJMra1401483] [PMID: 29320652]
[4]
Gianfrancesco MA, Stridh P, Shao X, et al. Genetic risk factors for pediatric-onset multiple sclerosis. Mult Scler 2018; 24(14): 1825-34.
[http://dx.doi.org/10.1177/1352458517733551] [PMID: 28980494]
[5]
Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: An umbrella review of systematic reviews and meta-analyses. Lancet Neurol 2015; 14(3): 263-73.
[http://dx.doi.org/10.1016/S1474-4422(14)70267-4] [PMID: 25662901]
[6]
O’Gorman C, Lin R, Stankovich J, Broadley SA. Modelling genetic susceptibility to multiple sclerosis with family data. Neuroepidemiology 2013; 40(1): 1-12.
[http://dx.doi.org/10.1159/000341902] [PMID: 23075677]
[7]
Khondkarian OA, Zavalishin IA, Nevskaia OM. Classification of multiple sclerosis. Zh Nevropatol Psikhiatr Im S S Korsakova 1983; 83(2): 164-6.
[PMID: 6858474]
[8]
Noseworthy JH. Progress in determining the causes and treatment of multiple sclerosis. Nature 1999; 399(6738) (Suppl.): A40-7.
[http://dx.doi.org/10.1038/399a040] [PMID: 10392579]
[9]
Segal BM. Stage-specific immune dysregulation in multiple sclerosis. J Interferon Cytokine Res 2014; 34(8): 633-40.
[http://dx.doi.org/10.1089/jir.2014.0025] [PMID: 25084180]
[10]
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83(3): 278-86.
[http://dx.doi.org/10.1212/WNL.0000000000000560] [PMID: 24871874]
[11]
Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine 2017; 16: 41-50.
[http://dx.doi.org/10.1016/j.ebiom.2017.01.042] [PMID: 28161400]
[12]
Goldenberg MM. Multiple sclerosis review. P&T 2012; 37(3): 175-84.
[PMID: 22605909]
[13]
Jeker LT, Bluestone JA. MicroRNA regulation of T-cell differentiation and function. Immunol Rev 2013; 253(1): 65-81.
[http://dx.doi.org/10.1111/imr.12061] [PMID: 23550639]
[14]
Zhou S, Dong X, Zhang C, et al. MicroRNAs are implicated in the suppression of CD4+CD25−conventional T cell proliferation by CD4+CD25+ regulatory T cells. Mol Immunol 2015; 63(2): 464-72.
[http://dx.doi.org/10.1016/j.molimm.2014.10.001] [PMID: 25457879]
[15]
Yang L, Boldin MP, Yu Y, et al. miR-146a controls the resolution of T cell responses in mice. J Exp Med 2012; 209(9): 1655-70.
[http://dx.doi.org/10.1084/jem.20112218] [PMID: 22891274]
[16]
Goldmann T, Prinz M. Role of microglia in CNS autoimmunity. Clinical and Developmental Immunology 2013.
[http://dx.doi.org/10.1155/2013/208093]
[17]
Chastain EM, d’Anne SD, Rodgers JM, Miller SD. The role of antigen presenting cells in multiple sclerosis. Biochimica et Biophysica Acta (BBA)-. Biochim Biophys Acta Mol Basis Dis 2011; 1812(2): 265-74.
[http://dx.doi.org/10.1016/j.bbadis.2010.07.008]
[18]
Kipp M, van der Star B, Vogel DY, et al. Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond. Mult Scler Relat Disord 2012; 1(1): 15-28.
[http://dx.doi.org/10.1016/j.msard.2011.09.002] [PMID: 25876447]
[19]
Baecher-Allan C, Viglietta V, Hafler DA, Eds. Human CD4+ CD25+ regulatory T cells. Seminars in immunology. Elsevier 2004.
[20]
Goldschmidt T, Antel J, König FB, Brück W, Kuhlmann T. Remyelination capacity of the MS brain decreases with disease chronicity. Neurology 2009; 72(22): 1914-21.
[http://dx.doi.org/10.1212/WNL.0b013e3181a8260a] [PMID: 19487649]
[21]
Pozniak CD, Langseth AJ, Dijkgraaf GJ, Choe Y, Werb Z, Pleasure SJ. Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing Suppressor of Fused expression. Proc Natl Acad Sci USA 2010; 107(50): 21795-800.
[http://dx.doi.org/10.1073/pnas.1016485107] [PMID: 21098272]
[22]
Scaglione A, Patzig J, Liang J, et al. PRMT5-mediated regulation of developmental myelination. Nat Commun 2018; 9(1): 2840.
[http://dx.doi.org/10.1038/s41467-018-04863-9] [PMID: 30026560]
[23]
Zhang S, Zhu X, Gui X, et al. Sox2 is essential for oligodendroglial proliferation and differentiation during postnatal brain myelination and CNS remyelination. J Neurosci 2018; 38(7): 1802-20.
[http://dx.doi.org/10.1523/JNEUROSCI.1291-17.2018] [PMID: 29335358]
[24]
Ebrahimkhani S, Beadnall HN, Wang C, et al. Serum exosome microRNAs predict multiple sclerosis disease activity after fingolimod treatment. Mol Neurobiol 2020; 57(2): 1245-58.
[http://dx.doi.org/10.1007/s12035-019-01792-6] [PMID: 31721043]
[25]
Venkatesha SH, Dudics S, Song Y, Mahurkar A, Moudgil KD. The miRNA expression profile of experimental autoimmune encephalomyelitis reveals novel potential disease biomarkers. Int J Mol Sci 2018; 19(12): 3990.
[http://dx.doi.org/10.3390/ijms19123990] [PMID: 30544973]
[26]
Thamilarasan M, Koczan D, Hecker M, Paap B, Zettl UK. MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun Rev 2012; 11(3): 174-9.
[http://dx.doi.org/10.1016/j.autrev.2011.05.009] [PMID: 21621006]
[27]
Eulalio A, Huntzinger E, Izaurralde E. Getting to the root of miRNA-mediated gene silencing. Cell 2008; 132(1): 9-14.
[http://dx.doi.org/10.1016/j.cell.2007.12.024] [PMID: 18191211]
[28]
Wu L, Belasco JG. Let me count the ways: Mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell 2008; 29(1): 1-7.
[http://dx.doi.org/10.1016/j.molcel.2007.12.010] [PMID: 18206964]
[29]
Rahban D, Mohammadi F, Alidadi M, Ghantabpour T, Kheyli PAG, Ahmadi M. Genetic polymorphisms and epigenetic regulation of survivin encoding gene, BIRC5, in multiple sclerosis patients. BMC Immunol 2019; 20(1): 30.
[http://dx.doi.org/10.1186/s12865-019-0312-1] [PMID: 31438837]
[30]
Xu L, Yang BF, Ai J. MicroRNA transport: A new way in cell communication. J Cell Physiol 2013; 228(8): 1713-9.
[http://dx.doi.org/10.1002/jcp.24344] [PMID: 23460497]
[31]
Schwarzenbach H, Gahan PB. MicroRNA shuttle from cell-to-cell by exosomes and its impact in cancer. Noncoding RNA 2019; 5(1): 28.
[http://dx.doi.org/10.3390/ncrna5010028] [PMID: 30901915]
[32]
Madadi S, Schwarzenbach H, Saidijam M, Mahjub R, Soleimani M. Potential microRNA-related targets in clearance pathways of amyloid-β: Novel therapeutic approach for the treatment of Alzheimer’s disease. Cell Biosci 2019; 9(1): 91.
[http://dx.doi.org/10.1186/s13578-019-0354-3] [PMID: 31749959]
[33]
Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol 2014; 11(3): 145-56.
[http://dx.doi.org/10.1038/nrclinonc.2014.5] [PMID: 24492836]
[34]
Carlesi C, Ienco EC, Mancuso M, Siciliano G. Amyotrophic lateral sclerosis: A genetic point of view. Curr Mol Med 2014; 14(8): 1089-101.
[http://dx.doi.org/10.2174/1566524014666141010155822] [PMID: 25323864]
[35]
Madadi S, Saidijam M, Yavari B, Soleimani M. Downregulation of serum miR-106b: A potential biomarker for Alzheimer disease. Arch Physiol Biochem 2020; 1-5. Online ahead of print.
[http://dx.doi.org/10.1080/13813455.2020.1734842] [PMID: 32141790]
[36]
Madadi S, Soleimani M. Comparison of miR-16 and cel-miR-39 as reference controls for serum miRNA normalization in colorectal cancer. J Cell Biochem 2019; 120(4): 4802-3.
[http://dx.doi.org/10.1002/jcb.28174] [PMID: 30609138]
[37]
Fenoglio C, Ridolfi E, Galimberti D, Scarpini E. MicroRNAs as active players in the pathogenesis of multiple sclerosis. Int J Mol Sci 2012; 13(10): 13227-39.
[http://dx.doi.org/10.3390/ijms131013227] [PMID: 23202949]
[38]
Ha T-Y. The role of microRNAs in regulatory T cells and in the immune response. Immune Netw 2011; 11(1): 11-41.
[http://dx.doi.org/10.4110/in.2011.11.1.11] [PMID: 21494372]
[39]
Torabi S, Tamaddon M, Asadolahi M, et al. miR-455-5p downregulation promotes inflammation pathways in the relapse phase of relapsing-remitting multiple sclerosis disease. Immunogenetics 2019; 71(2): 87-95.
[http://dx.doi.org/10.1007/s00251-018-1087-x] [PMID: 30310937]
[40]
Liu Q, Gao Q, Zhang Y, Li Z, Mei X. MicroRNA-590 promotes pathogenic Th17 cell differentiation through targeting Tob1 and is associated with multiple sclerosis. Biochem Biophys Res Commun 2017; 493(2): 901-8.
[http://dx.doi.org/10.1016/j.bbrc.2017.09.123] [PMID: 28947212]
[41]
Waschbisch A, Atiya M, Linker RA, Potapov S, Schwab S, Derfuss T. Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis. PLoS One 2011; 6(9): e24604.
[http://dx.doi.org/10.1371/journal.pone.0024604] [PMID: 21949733]
[42]
Hecker M, Thamilarasan M, Koczan D, et al. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci 2013; 14(8): 16087-110.
[http://dx.doi.org/10.3390/ijms140816087] [PMID: 23921681]
[43]
Liu S, Ren C, Qu X, et al. miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1. Eur J Neurosci 2017; 45(2): 249-59.
[http://dx.doi.org/10.1111/ejn.13485] [PMID: 27873367]
[44]
Wang H, Moyano AL, Ma Z, et al. miR-219 cooperates with miR-338 in myelination and promotes myelin repair in the CNS. Dev Cell 2017; 40(6): 566-582.e5.
[http://dx.doi.org/10.1016/j.devcel.2017.03.001] [PMID: 28350989]
[45]
Pusic AD, Kraig RP. Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. Glia 2014; 62(2): 284-99.
[http://dx.doi.org/10.1002/glia.22606] [PMID: 24339157]
[46]
Du C, Liu C, Kang J, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 2009; 10(12): 1252-9.
[http://dx.doi.org/10.1038/ni.1798] [PMID: 19838199]
[47]
Liu S, Rezende RM, Moreira TG, et al. Oral administration of miR-30d from feces of MS patients suppresses MS-like symptoms in mice by expanding Akkermansia muciniphila. Cell Host Microbe 2019; 26(6): 779-794.e8.
[http://dx.doi.org/10.1016/j.chom.2019.10.008] [PMID: 31784260]
[48]
Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain 2004; 127(Pt 7): 1463-78.
[http://dx.doi.org/10.1093/brain/awh176] [PMID: 15180926]
[49]
Hunter MP, Ismail N, Zhang X, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 2008; 3(11): e3694.
[http://dx.doi.org/10.1371/journal.pone.0003694] [PMID: 19002258]
[50]
Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18(10): 997-1006.
[http://dx.doi.org/10.1038/cr.2008.282] [PMID: 18766170]
[51]
Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30): 10513-8.
[http://dx.doi.org/10.1073/pnas.0804549105] [PMID: 18663219]
[52]
Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 2008; 10(4): R101.
[http://dx.doi.org/10.1186/ar2493] [PMID: 18759964]
[53]
Fattahi M, Rezaei N, Nematalahi FS, et al. MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis. Mult Scler Relat Disord 2019; 35: 241-5.
[http://dx.doi.org/10.1016/j.msard.2019.07.034] [PMID: 31421628]
[54]
Fattahi M, Eskandari N, Sotoodehnejadnematalahi F, Shaygannejad V, Kazemi M. Comparison of the expression of miR-326 between interferon beta responders and non-responders in relapsing-remitting multiple sclerosis. Cell J 2020; 22(1): 92-5.
[PMID: 31606972]
[55]
Mancuso R, Hernis A, Agostini S, Rovaris M, Caputo D, Clerici M. MicroRNA-572 expression in multiple sclerosis patients with different patterns of clinical progression. J Transl Med 2015; 13(1): 148.
[http://dx.doi.org/10.1186/s12967-015-0504-2] [PMID: 25947625]
[56]
Groen K, Maltby VE, Lea RA, et al. Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis. BMC Med Genomics 2018; 11(1): 48.
[http://dx.doi.org/10.1186/s12920-018-0365-7] [PMID: 29783973]
[57]
Keller A, Leidinger P, Lange J, et al. Multiple sclerosis: MicroRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One 2009; 4(10): e7440.
[http://dx.doi.org/10.1371/journal.pone.0007440] [PMID: 19823682]
[58]
Mycko MP, Baranzini SE. microRNA and exosome profiling in multiple sclerosis. Mult Scler 2020; 26(5): 599-604.
[http://dx.doi.org/10.1177/1352458519879303] [PMID: 31965891]
[59]
Manna I, Iaccino E, Dattilo V, et al. Exosome-associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients. FASEB J 2018; 32(8): 4241-6.
[http://dx.doi.org/10.1096/fj.201701533R] [PMID: 29505299]
[60]
Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep 2017; 7(1): 14293.
[http://dx.doi.org/10.1038/s41598-017-14301-3] [PMID: 29084979]
[61]
Emery B, Lu QR. Transcriptional and epigenetic regulation of oligodendrocyte development and myelination in the central nervous system. Cold Spring Harb Perspect Biol 2015; 7(9): a020461.
[http://dx.doi.org/10.1101/cshperspect.a020461] [PMID: 26134004]
[62]
Guo F, Lang J, Sohn J, Hammond E, Chang M, Pleasure D. Canonical Wnt signaling in the oligodendroglial lineage--puzzles remain. Glia 2015; 63(10): 1671-93.
[http://dx.doi.org/10.1002/glia.22813] [PMID: 25782433]
[63]
Suo N, Guo YE, He B, Gu H, Xie X. Inhibition of MAPK/ERK pathway promotes oligodendrocytes generation and recovery of demyelinating diseases. Glia 2019; 67(7): 1320-32.
[http://dx.doi.org/10.1002/glia.23606] [PMID: 30815939]
[64]
Tripathi A, Volsko C, Garcia JP, et al. Oligodendrocyte intrinsic miR-27a controls myelination and remyelination. Cell Rep 2019; 29(4): 904-919.e9.
[http://dx.doi.org/10.1016/j.celrep.2019.09.020] [PMID: 31644912]
[65]
Lecca D, Marangon D, Coppolino GT, et al. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically upregulated in human multiple sclerosis. Sci Rep 2016; 6(1): 1-12.
[http://dx.doi.org/10.1038/srep34503] [PMID: 28442746]
[66]
Zhang J, Zhang ZG, Lu M, Zhang Y, Shang X, Chopp M. MiR-146a promotes oligodendrocyte progenitor cell differentiation and enhances remyelination in a model of experimental autoimmune encephalomyelitis. Neurobiol Dis 2019; 125: 154-62.
[http://dx.doi.org/10.1016/j.nbd.2019.01.019] [PMID: 30707940]
[67]
Tripathi A, Volsko C, Datta U, Regev K, Dutta R. Expression of disease-related miRNAs in white-matter lesions of progressive multiple sclerosis brains. Ann Clin Transl Neurol 2019; 6(5): 854-62.
[http://dx.doi.org/10.1002/acn3.750] [PMID: 31139683]
[68]
Deneen B, Ho R, Lukaszewicz A, Hochstim CJ, Gronostajski RM, Anderson DJ. The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron 2006; 52(6): 953-68.
[http://dx.doi.org/10.1016/j.neuron.2006.11.019] [PMID: 17178400]
[69]
Glasgow SM, Zhu W, Stolt CC, et al. Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes. Nat Neurosci 2014; 17(10): 1322-9.
[http://dx.doi.org/10.1038/nn.3790] [PMID: 25151262]
[70]
Mi S, Hu B, Hahm K, et al. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat Med 2007; 13(10): 1228-33.
[http://dx.doi.org/10.1038/nm1664] [PMID: 17906634]
[71]
Morrison BM, Lee Y, Rothstein JD. Oligodendroglia: Metabolic supporters of axons. Trends Cell Biol 2013; 23(12): 644-51.
[http://dx.doi.org/10.1016/j.tcb.2013.07.007] [PMID: 23988427]
[72]
Martin NA, Molnar V, Szilagyi GT, et al. Experimental demyelination and axonal loss are reduced in MicroRNA-146a deficient mice. Front Immunol 2018; 9: 490.
[http://dx.doi.org/10.3389/fimmu.2018.00490] [PMID: 29593734]
[73]
Choe Y, Huynh T, Pleasure SJ. Migration of oligodendrocyte progenitor cells is controlled by transforming growth factor β family proteins during corticogenesis. J Neurosci 2014; 34(45): 14973-83.
[http://dx.doi.org/10.1523/JNEUROSCI.1156-14.2014] [PMID: 25378163]
[74]
Pedraza CE, Taylor C, Pereira A, et al. Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase. ASN Neuro 2014; 6(4): 1759091414538134.
[http://dx.doi.org/10.1177/1759091414538134] [PMID: 25289646]
[75]
Rizo J, Südhof TC. The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged? Annu Rev Cell Dev Biol 2012; 28(1): 279-308.
[http://dx.doi.org/10.1146/annurev-cellbio-101011-155818] [PMID: 23057743]
[76]
Compston A, Coles A. Multiple sclerosis. The Lancet 2008; 372(9648): 1502-17.
[http://dx.doi.org/10.1016/S0140-6736(08)61620-7]
[77]
Broux B, Stinissen P, Hellings N. Which immune cells matter? The immunopathogenesis of multiple sclerosis. Crit Rev in Immunol 2013; 33(4): 283-306.
[http://dx.doi.org/10.1615/CritRevImmunol.2013007453]
[78]
Jin X-F, Wu N, Wang L, Li J. Circulating microRNAs: A novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases. Cell Mol Neurobiol 2013; 33(5): 601-13.
[http://dx.doi.org/10.1007/s10571-013-9940-9] [PMID: 23633081]
[79]
Sanders KA, Benton MC, Lea RA, et al. Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells. Clin Epigenetics 2016; 8(1): 87.
[http://dx.doi.org/10.1186/s13148-016-0253-y] [PMID: 27570566]
[80]
Gandy KAO, Zhang J, Nagarkatti P, Nagarkatti M. Resveratrol (3, 5, 4′-Trihydroxy-trans-Stilbene) attenuates a mouse model of multiple sclerosis by altering the miR-124/sphingosine kinase 1 axis in encephalitogenic T cells in the brain. J Neuroimmune Pharmacol 2019; 14(3): 462-77.
[http://dx.doi.org/10.1007/s11481-019-09842-5] [PMID: 30941623]
[81]
Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nat Med 2011; 17(1): 64-70.
[http://dx.doi.org/10.1038/nm.2266] [PMID: 21131957]
[82]
Zhao Y, Ling Z, Hao Y, et al. MiR-124 acts as a tumor suppressor by inhibiting the expression of sphingosine kinase 1 and its downstream signaling in head and neck squamous cell carcinoma. Oncotarget 2017; 8(15): 25005-20.
[http://dx.doi.org/10.18632/oncotarget.15334] [PMID: 28212569]
[83]
Zhou Y, Han Y, Zhang Z, et al. MicroRNA-124 upregulation inhibits proliferation and invasion of osteosarcoma cells by targeting sphingosine kinase 1. Hum Cell 2017; 30(1): 30-40.
[http://dx.doi.org/10.1007/s13577-016-0148-4] [PMID: 27743351]
[84]
Azimi M, Ghabaee M, Naser Moghadasi A, Izad M. Altered expression of miR-326 in T cell-derived exosomes of patients with relapsing-remitting multiple sclerosis. Iran J Allergy Asthma Immunol 2019; 18(1): 108-13.
[http://dx.doi.org/10.18502/ijaai.v18i1.636] [PMID: 30848579]
[85]
Zhang Z, Xue Z, Liu Y, et al. MicroRNA-181c promotes Th17 cell differentiation and mediates experimental autoimmune encephalomyelitis. Brain Behav Immun 2018; 70: 305-14.
[http://dx.doi.org/10.1016/j.bbi.2018.03.011] [PMID: 29545117]
[86]
Majd M, Hosseini A, Ghaedi K, et al. MiR-9-5p and miR-106a-5p dysregulated in CD4+ T-cells of multiple sclerosis patients and targeted essential factors of T helper17/regulatory T-cells differentiation. Iran J Basic Med Sci 2018; 21(3): 277-83.
[PMID: 29511494]
[87]
Wu R, He Q, Chen H, et al. MicroRNA-448 promotes multiple sclerosis development through induction of Th17 response through targeting protein tyrosine phosphatase non-receptor type 2 (PTPN2). Biochem Biophys Res Commun 2017; 486(3): 759-66.
[http://dx.doi.org/10.1016/j.bbrc.2017.03.115] [PMID: 28342869]
[88]
Liu R, Ma X, Chen L, et al. MicroRNA-15b suppresses Th17 differentiation and is associated with pathogenesis of multiple sclerosis by targeting O-GlcNAc transferase. J Immunol 2017; 198(7): 2626-39.
[http://dx.doi.org/10.4049/jimmunol.1601727] [PMID: 28228555]
[89]
Talebi F, Ghorbani S, Chan WF, et al. MicroRNA-142 regulates inflammation and T cell differentiation in an animal model of multiple sclerosis. J Neuroinflammation 2017; 14(1): 55.
[http://dx.doi.org/10.1186/s12974-017-0832-7] [PMID: 28302134]
[90]
Wan C, Bi W, Lin P, et al. MicroRNA 182 promotes T helper 1 cell by repressing hypoxia induced factor 1 alpha in experimental autoimmune encephalomyelitis. Eur J Immunol 2019; 49(12): 2184-94.
[http://dx.doi.org/10.1002/eji.201948111] [PMID: 31411745]
[91]
Rezaei N, Talebi F, Ghorbani S, et al. MicroRNA-92a drives Th1 responses in the experimental autoimmune encephalomyelitis. Inflammation 2019; 42(1): 235-45.
[http://dx.doi.org/10.1007/s10753-018-0887-3] [PMID: 30411211]
[92]
Cantoni C, Cignarella F, Ghezzi L, et al. Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol 2017; 133(1): 61-77.
[http://dx.doi.org/10.1007/s00401-016-1621-6] [PMID: 27704281]
[93]
Satoorian T, Li B, Tang X, et al. MicroRNA223 promotes pathogenic T-cell development and autoimmune inflammation in central nervous system in mice. Immunology 2016; 148(4): 326-38.
[http://dx.doi.org/10.1111/imm.12611] [PMID: 27083389]
[94]
Kimura K, Hohjoh H, Fukuoka M, et al. Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis. Nat Commun 2018; 9(1): 17.
[http://dx.doi.org/10.1038/s41467-017-02406-2] [PMID: 29295981]
[95]
Hoye ML, Archambault AS, Gordon TM, et al. MicroRNA signature of central nervous system-infiltrating dendritic cells in an animal model of multiple sclerosis. Immunology 2018; 155(1): 112-22.
[http://dx.doi.org/10.1111/imm.12934] [PMID: 29749614]
[96]
Liu X, Zhou F, Yang Y, et al. MiR-409-3p and MiR-1896 co-operatively participate in IL-17-induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling. Glia 2019; 67(1): 101-12.
[http://dx.doi.org/10.1002/glia.23530] [PMID: 30294880]
[97]
Liu X, He F, Pang R, et al. Interleukin-17 (IL-17)-induced microRNA 873 (miR-873) contributes to the pathogenesis of experimental autoimmune encephalomyelitis by targeting A20 ubiquitin-editing enzyme. J Biol Chem 2014; 289(42): 28971-86.
[http://dx.doi.org/10.1074/jbc.M114.577429] [PMID: 25183005]
[98]
Galloway DA, Blandford SN, Berry T, et al. miR-223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system. Glia 2019; 67(5): 857-69.
[http://dx.doi.org/10.1002/glia.23576] [PMID: 30548333]
[99]
Junker A, Krumbholz M, Eisele S, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009; 132(Pt 12): 3342-52.
[http://dx.doi.org/10.1093/brain/awp300] [PMID: 19952055]
[100]
Amedei A, Prisco D, D’Elios MM. Multiple sclerosis: The role of cytokines in pathogenesis and in therapies. Int J Mol Sci 2012; 13(10): 13438-60.
[http://dx.doi.org/10.3390/ijms131013438] [PMID: 23202961]
[101]
McFarland HF, Martin R. Multiple sclerosis: A complicated picture of autoimmunity. Nat Immunol 2007; 8(9): 913-9.
[http://dx.doi.org/10.1038/ni1507] [PMID: 17712344]
[102]
Braverman J, Sogi KM, Benjamin D, Nomura DK, Stanley SA. HIF-1α is an essential mediator of IFN-γ–dependent immunity to Mycobacterium tuberculosis. J Immunol 2016; 197(4): 1287-97.
[http://dx.doi.org/10.4049/jimmunol.1600266] [PMID: 27430718]
[103]
Bhattacharyya S, Zhao Y, Kay TW, Muglia LJ. Glucocorticoids target Suppressor Of Cytokine Signaling 1 (SOCS1) and type 1 interferons to regulate Toll-like receptor-induced STAT1 activation. Proc Natl Acad Sci USA 2011; 108(23): 9554-9.
[http://dx.doi.org/10.1073/pnas.1017296108] [PMID: 21606371]
[104]
Takahashi R, Nishimoto S, Muto G, et al. SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-γ and IL-17A production. J Exp Med 2011; 208(10): 2055-67.
[http://dx.doi.org/10.1084/jem.20110428] [PMID: 21893603]
[105]
Zhou X, Bailey-Bucktrout SL, Jeker LT, et al. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol 2009; 10(9): 1000-7.
[http://dx.doi.org/10.1038/ni.1774] [PMID: 19633673]
[106]
Heupel K, Sargsyan V, Plomp JJ, et al. Loss of transforming growth factor-beta 2 leads to impairment of central synapse function. Neural Dev 2008; 3(1): 25.
[http://dx.doi.org/10.1186/1749-8104-3-25] [PMID: 18854036]
[107]
Diemel LT, Jackson SJ, Cuzner ML. Role for TGF-β1, FGF-2 and PDGF-AA in a myelination of CNS aggregate cultures enriched with macrophages. J Neurosci Res 2003; 74(6): 858-67.
[http://dx.doi.org/10.1002/jnr.10837] [PMID: 14648590]
[108]
Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 2010; 11(1): 7-13.
[http://dx.doi.org/10.1038/ni.1818] [PMID: 20016504]
[109]
Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. A role for TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol 2001; 166(12): 7282-9.
[http://dx.doi.org/10.4049/jimmunol.166.12.7282] [PMID: 11390478]
[110]
Zheng SG, Gray JD, Ohtsuka K, Yamagiwa S, Horwitz DA. Generation ex vivo of TGF-β-producing regulatory T cells from CD4+CD25- precursors. J Immunol 2002; 169(8): 4183-9.
[http://dx.doi.org/10.4049/jimmunol.169.8.4183] [PMID: 12370347]
[111]
Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J Exp Med 2003; 198(12): 1875-86.
[http://dx.doi.org/10.1084/jem.20030152] [PMID: 14676299]
[112]
Severin ME, Lee PW, Liu Y, et al. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis. Brain 2016; 139(Pt 6): 1747-61.
[http://dx.doi.org/10.1093/brain/aww084] [PMID: 27190026]
[113]
Liu S, da Cunha AP, Rezende RM, et al. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 2016; 19(1): 32-43.
[http://dx.doi.org/10.1016/j.chom.2015.12.005] [PMID: 26764595]
[114]
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7(1): 12015.
[http://dx.doi.org/10.1038/ncomms12015] [PMID: 27352007]
[115]
Chen J, Chia N, Kalari KR, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016; 6(1): 28484.
[http://dx.doi.org/10.1038/srep28484] [PMID: 27346372]
[116]
Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol 2009; 27(1): 485-517.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132710] [PMID: 19132915]
[117]
Dong C. TH17 cells in development: An updated view of their molecular identity and genetic programming. Nat Rev Immunol 2008; 8(5): 337-48.
[http://dx.doi.org/10.1038/nri2295] [PMID: 18408735]
[118]
Veldhoen M, Hirota K, Westendorf AM, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008; 453(7191): 106-9.
[http://dx.doi.org/10.1038/nature06881] [PMID: 18362914]
[119]
Brüstle A, Heink S, Huber M, et al. The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 2007; 8(9): 958-66.
[http://dx.doi.org/10.1038/ni1500] [PMID: 17676043]
[120]
Zhou L, Lopes JE, Chong MM, et al. TGF-β-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008; 453(7192): 236-40.
[http://dx.doi.org/10.1038/nature06878] [PMID: 18368049]
[121]
Moisan J, Grenningloh R, Bettelli E, Oukka M, Ho IC. Ets-1 is a negative regulator of Th17 differentiation. J Exp Med 2007; 204(12): 2825-35.
[http://dx.doi.org/10.1084/jem.20070994] [PMID: 17967903]
[122]
Mangan PR, Harrington LE, O’Quinn DB, et al. Transforming growth factor-β induces development of the T(H)17 lineage. Nature 2006; 441(7090): 231-4.
[http://dx.doi.org/10.1038/nature04754] [PMID: 16648837]
[123]
Spalinger MR, Kasper S, Chassard C, et al. PTPN2 controls differentiation of CD4⁺ T cells and limits intestinal inflammation and intestinal dysbiosis. Mucosal Immunol 2015; 8(4): 918-29.
[http://dx.doi.org/10.1038/mi.2014.122] [PMID: 25492475]
[124]
Bulatov E, Khaiboullina S, dos Reis HJ, et al. Ubiquitin-proteasome system: Promising therapeutic targets in autoimmune and neurodegenerative diseases. Bionanoscience 2016; 6(4): 341-4.
[http://dx.doi.org/10.1007/s12668-016-0233-x]
[125]
Giles DA, Washnock-Schmid JM, Duncker PC, et al. Myeloid cell plasticity in the evolution of central nervous system autoimmunity. Ann Neurol 2018; 83(1): 131-41.
[http://dx.doi.org/10.1002/ana.25128] [PMID: 29283442]
[126]
Lloyd AF, Miron VE. Cellular and molecular mechanisms underpinning macrophage activation during remyelination. Front Cell Dev Biol 2016; 4: 60.
[http://dx.doi.org/10.3389/fcell.2016.00060] [PMID: 27446913]
[127]
Miron VE, Boyd A, Zhao J-W, et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 2013; 16(9): 1211-8.
[http://dx.doi.org/10.1038/nn.3469] [PMID: 23872599]
[128]
Ishikawa-Sekigami T, Kaneko Y, Okazawa H, et al. SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages. Blood 2006; 107(1): 341-8.
[http://dx.doi.org/10.1182/blood-2005-05-1896] [PMID: 16141346]
[129]
Fritsche L, Teuber-Hanselmann S, Soub D, Harnisch K, Mairinger F, Junker A. MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin-7. Brain Pathol 2020; 30(3): 524-40.
[http://dx.doi.org/10.1111/bpa.12800] [PMID: 31663645]
[130]
Shapoori S, Ganjalikhani-Hakemi M, Rezaeepoor M, et al. Negative Regulation of Semaphorin-3A expression in peripheral blood mononuclear cells using microRNA-497-5p. Iran J Med Sci 2019; 44(4): 325-33.
[PMID: 31439976]
[131]
Aung LL, Mouradian MM, Dhib-Jalbut S, Balashov KE. MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by microRNA-320a. J Neuroimmunol 2015; 278: 185-9.
[http://dx.doi.org/10.1016/j.jneuroim.2014.11.004] [PMID: 25468268]
[132]
Vadasz Z, Haj T, Halasz K, et al. Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosus. Arthritis Res Ther 2012; 14(3): R146.
[http://dx.doi.org/10.1186/ar3881] [PMID: 22697500]
[133]
Kou K, Nakamura F, Aihara M, et al. Decreased expression of semaphorin-3A, a neurite-collapsing factor, is associated with itch in psoriatic skin. Acta Derm Venereol 2012; 92(5): 521-8.
[http://dx.doi.org/10.2340/00015555-1350] [PMID: 22565412]
[134]
Catalano A. The neuroimmune semaphorin-3A reduces inflammation and progression of experimental autoimmune arthritis. J Immunol 2010; 185(10): 6373-83.
[http://dx.doi.org/10.4049/jimmunol.0903527] [PMID: 20937848]
[135]
Rimar D, Nov Y, Rosner I, et al. Semaphorin 3A: An immunoregulator in systemic sclerosis. Rheumatol Int 2015; 35(10): 1625-30.
[http://dx.doi.org/10.1007/s00296-015-3269-2] [PMID: 25895648]
[136]
Takagawa S, Nakamura F, Kumagai K, Nagashima Y, Goshima Y, Saito T. Decreased semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis. BMC Musculoskelet Disord 2013; 14(1): 40.
[http://dx.doi.org/10.1186/1471-2474-14-40] [PMID: 23343469]
[137]
Vadasz Z, Toubi E. Semaphorins: Their dual role in regulating immune-mediated diseases. Clin Rev Allergy Immunol 2014; 47(1): 17-25.
[http://dx.doi.org/10.1007/s12016-013-8360-4] [PMID: 23397481]
[138]
Lepelletier Y, Moura IC, Hadj-Slimane R, et al. Immunosuppressive role of semaphorin-3A on T cell proliferation is mediated by inhibition of actin cytoskeleton reorganization. Eur J Immunol 2006; 36(7): 1782-93.
[http://dx.doi.org/10.1002/eji.200535601] [PMID: 16791896]
[139]
Lindberg RL, Hoffmann F, Mehling M, Kuhle J, Kappos L. Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol 2010; 40(3): 888-98.
[http://dx.doi.org/10.1002/eji.200940032] [PMID: 20148420]
[140]
Rezaeepoor M, Ganjalikhani-Hakemi M, Shapoori S, et al. Semaphorin-3A as an immune modulator is suppressed by MicroRNA-145-5p. Cell J 2018; 20(1): 113-9.
[PMID: 29308627]
[141]
Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer 2003; 3(1): 46-54.
[http://dx.doi.org/10.1038/nrc968] [PMID: 12509766]
[142]
Mancuso R, Agostini S, Marventano I, Hernis A, Saresella M, Clerici M. NCAM1 is the target of miRNA-572: Validation in the human oligodendroglial cell line. Cell Mol Neurobiol 2018; 38(2): 431-40.
[http://dx.doi.org/10.1007/s10571-017-0486-0] [PMID: 28332001]
[143]
Zhang Y, Han JJ, Liang XY, et al. miR-23b suppresses leukocyte migration and pathogenesis of experimental autoimmune encephalomyelitis by targeting CCL7. Mol Ther 2018; 26(2): 582-92.
[http://dx.doi.org/10.1016/j.ymthe.2017.11.013] [PMID: 29275848]
[144]
Gharibi S, Moghimi B, Haghmorad D, et al. Altered expression patterns of complement factor H and miR-146a genes in acute-chronic phases in experimental autoimmune encephalomyelitis mouse. J Cell Physiol 2019; 234(11): 19842-51.
[http://dx.doi.org/10.1002/jcp.28583] [PMID: 30972735]
[145]
Potenza N, Mosca N, Mondola P, Damiano S, Russo A, De Felice B. Human miR-26a-5p regulates the glutamate transporter SLC1A1 (EAAT3) expression. Relevance in multiple sclerosis. Biochim Biophys Acta Mol Basis Dis 2018; 1864(1): 317-23.
[http://dx.doi.org/10.1016/j.bbadis.2017.09.024] [PMID: 28962897]
[146]
Mandolesi G, De Vito F, Musella A, et al. miR-142-3p is a key regulator of IL-1β-dependent synaptopathy in neuroinflammation. J Neurosci 2017; 37(3): 546-61.
[http://dx.doi.org/10.1523/JNEUROSCI.0851-16.2016] [PMID: 28100738]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy