Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

An Updated Review of Epigenetic-Related Mechanisms and their Contribution to Multiple Sclerosis Disease

Author(s): Maedeh Eslahi, Negin Nematbakhsh, Narges Dastmalchi, Shahram Teimourian and Reza Safaralizadeh*

Volume 22, Issue 3, 2023

Published on: 17 March, 2022

Page: [381 - 393] Pages: 13

DOI: 10.2174/1871527321666220119104649

open access plus

Abstract

Multiple Sclerosis (MS) is a multifactorial, neurodegenerative, and inflammatory demyelination disease with incomplete remyelination in the CNS. It would be more informative to reveal the underlying molecular mechanisms of MS. Molecular mechanisms involving epigenetic changes play a pivotal role in this disease. Epigenetic changes impact gene expression without altering the underlying DNA sequence. The main epigenetic modifications that play a key role in the regulation of gene expression principally include DNA methylation, histone modifications, and microRNA- associated post-transcriptional gene silencing. In this review, we summarize the dynamics of epigenetic changes and their relation to environmental risk factors in MS pathogenesis. Studies suggest that epigenetic changes have a role in the development of MS and environmental risk factors, such as vitamin D, smoking, and Epstein-Barr virus infection seem to influence the development and susceptibility to MS. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the diseases, which shows complicated pathogenesis. Epigenetic research has the potential to complete our understanding of MS initiation and progression. Increased understanding of MS molecular pathways leads to new insights into potential MS therapies. However, there is a need for in vivo evaluation of the role of epigenetic factors in MS therapy. It would be more valuable to indicate the role of various epigenetic factors in MS.

Keywords: Epigenetic mechanisms, multiple sclerosis, DNA methylation, histone modification, microRNAs, environmental risk factors.

[1]
Wildner P, Stasiołek M, Matysiak M. Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases. Mult Scler Relat Disord 2020; 37: 101452.
[http://dx.doi.org/10.1016/j.msard.2019.101452] [PMID: 31670010]
[2]
Macaron G, Ontaneda D. Diagnosis and management of progressive multiple sclerosis. Biomedicines 2019; 7(3): 7.
[http://dx.doi.org/10.3390/biomedicines7030056] [PMID: 31362384]
[3]
Klineova S, Lublin FD. Clinical course of multiple sclerosis. Cold Spring Harb Perspect Med 2018; 8(9): 8.
[http://dx.doi.org/10.1101/cshperspect.a028928] [PMID: 29358317]
[4]
Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun 2015; 64: 13-25.
[http://dx.doi.org/10.1016/j.jaut.2015.06.010] [PMID: 26142251]
[5]
Trerotola M, Relli V, Simeone P, Alberti S. Epigenetic inheritance and the missing heritability. Hum Genomics 2015; 9: 17.
[http://dx.doi.org/10.1186/s40246-015-0041-3] [PMID: 26216216]
[6]
Angeloni B, Bigi R, Bellucci G, et al. A case of double standard: Sex differences in multiple sclerosis risk factors. Int J Mol Sci 2021; 22(7): 22.
[http://dx.doi.org/10.3390/ijms22073696] [PMID: 33918133]
[7]
Tomasetti M, Gaetani S, Monaco F, Neuzil J, Santarelli L. Epigenetic regulation of miRNA expression in malignant mesothelioma: miRNAs as biomarkers of early diagnosis and therapy. Front Oncol 2019; 9: 1293.
[http://dx.doi.org/10.3389/fonc.2019.01293] [PMID: 31850200]
[8]
Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev 2021; 69: 101348.
[http://dx.doi.org/10.1016/j.arr.2021.101348] [PMID: 33930583]
[9]
Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology 2013; 38(1): 23-38.
[http://dx.doi.org/10.1038/npp.2012.112] [PMID: 22781841]
[10]
Gujar H, Weisenberger DJ, Liang G. The roles of human DNA methyltransferases and their isoforms in shaping the epigenome. Genes (Basel) 2019; 10(2): 10.
[http://dx.doi.org/10.3390/genes10020172] [PMID: 30813436]
[11]
Jin B, Robertson KD. DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol 2013; 754: 3-29.
[http://dx.doi.org/10.1007/978-1-4419-9967-2_1] [PMID: 22956494]
[12]
Tiane A, Schepers M, Riemens R, et al. DNA methylation regulates the expression of the negative transcriptional regulators ID2 and ID4 during OPC differentiation. Cell Mol Life Sci 2021; 78(19-20): 6631-44.
[http://dx.doi.org/10.1007/s00018-021-03927-2] [PMID: 34482420]
[13]
Tiane A, Schepers M, Rombaut B, et al. From OPC to oligodendrocyte: An epigenetic journey. Cells 2019; 8(10): 8.
[http://dx.doi.org/10.3390/cells8101236] [PMID: 31614602]
[14]
Mangano K, Fagone P, Bendtzen K, et al. Hypomethylating agent 5-aza-2′-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models. J Cell Physiol 2014; 229(12): 1918-25.
[http://dx.doi.org/10.1002/jcp.24641] [PMID: 24700487]
[15]
Ciccocioppo F, Lanuti P, Pierdomenico L, et al. The characterization of regulatory t-cell profiles in alzheimer’s disease and multiple sclerosis. Sci Rep 2019; 9(1): 8788.
[http://dx.doi.org/10.1038/s41598-019-45433-3] [PMID: 31217537]
[16]
Gacias M, Casaccia P. Epigenetic mechanisms in multiple sclerosis. Rev Esp Escler Múlt 2014; 6(29): 25-35.
[PMID: 30147811]
[17]
Kulakova OG, Kabilov MR, Danilova LV, et al. Whole-genome DNA methylation analysis of peripheral blood mononuclear cells in multiple sclerosis patients with different disease courses. Acta Nat (Engl Ed) 2016; 8(3): 103-10.
[http://dx.doi.org/10.32607/20758251-2016-8-3-103-110] [PMID: 27795849]
[18]
Rhead B, Brorson IS, Berge T, et al. Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. PLoS One 2018; 13(10): e0206511.
[http://dx.doi.org/10.1371/journal.pone.0206511] [PMID: 30379917]
[19]
Graves MC, Benton M, Lea RA, et al. Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis. Mult Scler 2014; 20(8): 1033-41.
[http://dx.doi.org/10.1177/1352458513516529] [PMID: 24336351]
[20]
Liu J, Zhu H, Wang H, et al. Methylation of secreted frizzled-related protein 1 (SFRP1) promoter downregulates Wnt/β-catenin activity in keloids. J Mol Histol 2018; 49(2): 185-93.
[http://dx.doi.org/10.1007/s10735-018-9758-3] [PMID: 29455276]
[21]
Fortress AM, Frick KM. Hippocampal Wnt signaling: Memory regulation and hormone interactions. Neuroscientist 2016; 22(3): 278-94.
[http://dx.doi.org/10.1177/1073858415574728] [PMID: 25717070]
[22]
Dutta R, Chomyk AM, Chang A, et al. Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors. Ann Neurol 2013; 73(5): 637-45.
[http://dx.doi.org/10.1002/ana.23860] [PMID: 23595422]
[23]
Chomyk AM, Volsko C, Tripathi A, et al. DNA methylation in demyelinated multiple sclerosis hippocampus. Sci Rep 2017; 7(1): 8696.
[http://dx.doi.org/10.1038/s41598-017-08623-5] [PMID: 28821749]
[24]
Celarain N, Tomas-Roig J. Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients. J Neuroinflammation 2020; 17(1): 21.
[http://dx.doi.org/10.1186/s12974-019-1667-1] [PMID: 31937331]
[25]
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21(3): 381-95.
[http://dx.doi.org/10.1038/cr.2011.22] [PMID: 21321607]
[26]
Cheng Y, He C, Wang M, et al. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther 2019; 4: 62.
[http://dx.doi.org/10.1038/s41392-019-0095-0] [PMID: 31871779]
[27]
Kim JK, Samaranayake M, Pradhan S. Epigenetic mechanisms in mammals. Cell Mol Life Sci 2009; 66(4): 596-612.
[http://dx.doi.org/10.1007/s00018-008-8432-4] [PMID: 18985277]
[28]
Miller JL, Grant PA. The role of DNA methylation and histone modifications in transcriptional regulation in humans. Subcell Biochem 2013; 61: 289-317.
[http://dx.doi.org/10.1007/978-94-007-4525-4_13] [PMID: 23150256]
[29]
Barter MJ, Bui C, Young DA. Epigenetic mechanisms in cartilage and osteoarthritis: DNA methylation, histone modifications and microRNAs. Osteoarthritis Cartilage 2012; 20(5): 339-49.
[http://dx.doi.org/10.1016/j.joca.2011.12.012] [PMID: 22281264]
[30]
Kallsen K, Andresen E, Heine H. Histone deacetylase (HDAC) 1 controls the expression of beta defensin 1 in human lung epithelial cells. PLoS One 2012; 7(11): e50000.
[http://dx.doi.org/10.1371/journal.pone.0050000] [PMID: 23185513]
[31]
Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci 2017; 18(7): 18.
[http://dx.doi.org/10.3390/ijms18071414] [PMID: 28671573]
[32]
Doñas C, Carrasco M, Fritz M, et al. The histone demethylase inhibitor GSK-J4 limits inflammation through the induction of a tolerogenic phenotype on DCs. J Autoimmun 2016; 75: 105-17.
[http://dx.doi.org/10.1016/j.jaut.2016.07.011] [PMID: 27528513]
[33]
Ramazi S, Allahverdi A, Zahiri J. Evaluation of post-translational modifications in histone proteins: A review on histone modification defects in developmental and neurological disorders. J Biosci 2020; 45: 135.
[http://dx.doi.org/10.1007/s12038-020-00099-2] [PMID: 33184251]
[34]
Sadakierska-Chudy A, Filip M. A comprehensive view of the epigenetic landscape. Part II: Histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs. Neurotox Res 2015; 27(2): 172-97.
[http://dx.doi.org/10.1007/s12640-014-9508-6] [PMID: 25516120]
[35]
Singh R, Chandel S, Dey D, et al. Epigenetic modification and therapeutic targets of diabetes mellitus. Biosci Rep 2020; 40(9): 40.
[http://dx.doi.org/10.1042/BSR20202160] [PMID: 32815547]
[36]
Licciardi PV, Karagiannis TC. Regulation of immune responses by histone deacetylase inhibitors. ISRN Hematol 2012; 2012: 690901.
[http://dx.doi.org/10.5402/2012/690901] [PMID: 22461998]
[37]
Singhal NK, Li S, Arning E, et al. Changes in methionine metabolism and histone h3 trimethylation are linked to mitochondrial defects in multiple sclerosis. J Neurosci 2015; 35(45): 15170-86.
[http://dx.doi.org/10.1523/JNEUROSCI.4349-14.2015] [PMID: 26558787]
[38]
Tahamtan A, Teymoori-Rad M, Nakstad B, Salimi V. Anti-Inflammatory MicroRNAs and their potential for inflammatory diseases treatment. Front Immunol 2018; 9: 1377.
[http://dx.doi.org/10.3389/fimmu.2018.01377] [PMID: 29988529]
[39]
Ksiazek-Winiarek DJ, Kacperska MJ, Glabinski A. MicroRNAs as novel regulators of neuroinflammation. Mediators Inflamm 2013; 2013: 172351.
[http://dx.doi.org/10.1155/2013/172351] [PMID: 23983402]
[40]
Huang J, Xu X, Yang J. miRNAs alter T helper 17 cell fate in the pathogenesis of autoimmune diseases. Front Immunol 2021; 12: 593473.
[http://dx.doi.org/10.3389/fimmu.2021.593473] [PMID: 33968012]
[41]
Küçükali CI, Kürtüncü M, Çoban A, Çebi M, Tüzün E. Epigenetics of multiple sclerosis: an updated review. Neuromolecular Med 2015; 17(2): 83-96.
[http://dx.doi.org/10.1007/s12017-014-8298-6] [PMID: 24652042]
[42]
Miljković D, Spasojević I. Multiple sclerosis: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal 2013; 19(18): 2286-334.
[http://dx.doi.org/10.1089/ars.2012.5068] [PMID: 23473637]
[43]
Kular L, Jagodic M. Epigenetic insights into multiple sclerosis disease progression. J Intern Med 2020; 288(1): 82-102.
[http://dx.doi.org/10.1111/joim.13045] [PMID: 32614160]
[44]
Ma X, Zhou J, Zhong Y, et al. Expression, regulation and function of microRNAs in multiple sclerosis. Int J Med Sci 2014; 11(8): 810-8.
[http://dx.doi.org/10.7150/ijms.8647] [PMID: 24936144]
[45]
Sethi A, Kulkarni N, Sonar S, Lal G. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance. Front Genet 2013; 4: 8.
[http://dx.doi.org/10.3389/fgene.2013.00008] [PMID: 23386861]
[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]
Gao Y, Han D, Feng J. MicroRNA in multiple sclerosis. Clin Chim Acta 2021; 516: 92-9.
[http://dx.doi.org/10.1016/j.cca.2021.01.020] [PMID: 33545109]
[48]
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]
[49]
Freiesleben S, Hecker M, Zettl UK, Fuellen G, Taher L. Analysis of microRNA and gene expression profiles in multiple sclerosis: Integrating interaction data to uncover regulatory mechanisms. Sci Rep 2016; 6: 34512.
[http://dx.doi.org/10.1038/srep34512] [PMID: 27694855]
[50]
de Faria O Jr, Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS. MicroRNA dysregulation in multiple sclerosis. Front Genet 2013; 3: 311.
[PMID: 23346094]
[51]
Chen C, Zhou Y, Wang J, Yan Y, Peng L, Qiu W. Dysregulated MicroRNA involvement in multiple sclerosis by induction of T helper 17 cell differentiation. Front Immunol 2018; 9: 1256.
[http://dx.doi.org/10.3389/fimmu.2018.01256] [PMID: 29915595]
[52]
Alfredsson L, Olsson T. Lifestyle and environmental factors in multiple sclerosis. Cold Spring Harb Perspect Med 2019; 9(4): 9.
[http://dx.doi.org/10.1101/cshperspect.a028944] [PMID: 29735578]
[53]
Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol 2019; 6(9): 1905-22.
[http://dx.doi.org/10.1002/acn3.50862] [PMID: 31392849]
[54]
Kočovská E, Gaughran F, Krivoy A, Meier UC. Vitamin-D deficiency as a potential environmental risk factor in multiple sclerosis, schizophrenia, and autism. Front Psychiatry 2017; 8: 47.
[http://dx.doi.org/10.3389/fpsyt.2017.00047] [PMID: 28396640]
[55]
Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: A comprehensive review. Neurol Ther 2018; 7(1): 59-85.
[http://dx.doi.org/10.1007/s40120-017-0086-4] [PMID: 29243029]
[56]
Wasnik S, Sharma I, Baylink DJ, Tang X. Vitamin D as a potential therapy for multiple sclerosis: Where are we? Int J Mol Sci 2020; 21(9): 21.
[http://dx.doi.org/10.3390/ijms21093102] [PMID: 32354174]
[57]
Karkeni E, Bonnet L, Marcotorchino J, et al. Vitamin D limits inflammation-linked microRNA expression in adipocytes in vitro and in vivo: A new mechanism for the regulation of inflammation by vitamin D. Epigenetics 2018; 13(2): 156-62.
[http://dx.doi.org/10.1080/15592294.2016.1276681] [PMID: 28055298]
[58]
Li YC, Chen Y, Liu W, Thadhani R. MicroRNA-mediated mechanism of vitamin D regulation of innate immune response. J Steroid Biochem Mol Biol 2014; 144 Pt A: 81-6.
[59]
Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol 2014; 5: 244.
[PMID: 25071589]
[60]
Pierrot-Deseilligny C, Rivaud-Péchoux S, Clerson P, de Paz R, Souberbielle JC. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Ther Adv Neurol Disord 2012; 5(4): 187-98.
[http://dx.doi.org/10.1177/1756285612447090] [PMID: 22783368]
[61]
Shoemaker TJ, Mowry EM. A review of vitamin D supplementation as disease-modifying therapy. Mult Scler 2018; 24(1): 6-11.
[http://dx.doi.org/10.1177/1352458517738131] [PMID: 29307295]
[62]
Handunnetthi L, Ramagopalan SV, Ebers GC. Multiple sclerosis, vitamin D, and HLA-DRB1*15. Neurology 2010; 74(23): 1905-10.
[http://dx.doi.org/10.1212/WNL.0b013e3181e24124] [PMID: 20530326]
[63]
Strzelak A, Ratajczak A, Adamiec A, Feleszko W. Tobacco smoke induces and alters immune responses in the lung triggering inflammation, allergy, asthma and other lung diseases: A mechanistic review. Int J Environ Res Public Health 2018; 15(5): 15.
[http://dx.doi.org/10.3390/ijerph15051033] [PMID: 29883409]
[64]
O’Gorman C, Lucas R, Taylor B. Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms. Int J Mol Sci 2012; 13(9): 11718-52.
[http://dx.doi.org/10.3390/ijms130911718] [PMID: 23109880]
[65]
Duffy CP, McCoy CE. The role of MicroRNAs in repair processes in multiple sclerosis. Cells 2020; 9(7): 9.
[http://dx.doi.org/10.3390/cells9071711] [PMID: 32708794]
[66]
Elfiky AM, Ahmed Mahmoud A, Zeidan HM, Mostafa Soliman M. Association between circulating microRNA-126 expression level and tumour necrosis factor alpha in healthy smokers. Biomarkers 2019; 24(5): 469-77.
[http://dx.doi.org/10.1080/1354750X.2019.1610497] [PMID: 31018714]
[67]
Zong D, Liu X, Li J, Ouyang R, Chen P. The role of cigarette smoke-induced epigenetic alterations in inflammation. Epigenetics Chromatin 2019; 12(1): 65.
[http://dx.doi.org/10.1186/s13072-019-0311-8] [PMID: 31711545]
[68]
Gao X, Thomsen H, Zhang Y, Breitling LP, Brenner H. The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes. Clin Epigenetics 2017; 9: 87.
[http://dx.doi.org/10.1186/s13148-017-0387-6] [PMID: 28824732]
[69]
Vogeley C, Esser C, Tüting T, Krutmann J, Haarmann-Stemmann T. Role of the aryl hydrocarbon receptor in environmentally induced skin aging and skin carcinogenesis. Int J Mol Sci 2019; 20(23): 20.
[http://dx.doi.org/10.3390/ijms20236005] [PMID: 31795255]
[70]
Ringh MV, Hagemann-Jensen M, Needhamsen M, et al. Tobacco smoking induces changes in true DNA methylation, hydroxymethylation and gene expression in bronchoalveolar lavage cells. EBioMedicine 2019; 46: 290-304.
[http://dx.doi.org/10.1016/j.ebiom.2019.07.006] [PMID: 31303497]
[71]
Hanssen-Bauer A, Solvang-Garten K, Akbari M, Otterlei M. X-ray repair cross complementing protein 1 in base excision repair. Int J Mol Sci 2012; 13(12): 17210-29.
[http://dx.doi.org/10.3390/ijms131217210] [PMID: 23247283]
[72]
Christiansen C, Castillo-Fernandez JE, Domingo-Relloso A, et al. Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects. Clin Epigenetics 2021; 13(1): 36.
[http://dx.doi.org/10.1186/s13148-021-01018-4] [PMID: 33593402]
[73]
Silva CP, Kamens HM. Cigarette smoke-induced alterations in blood: A review of research on DNA methylation and gene expression. Exp Clin Psychopharmacol 2021; 29(1): 116-35.
[http://dx.doi.org/10.1037/pha0000382] [PMID: 32658533]
[74]
Marabita F, Almgren M, Sjöholm LK, et al. Smoking induces DNA methylation changes in multiple sclerosis patients with exposure-response relationship. Sci Rep 2017; 7(1): 14589.
[http://dx.doi.org/10.1038/s41598-017-14788-w] [PMID: 29109506]
[75]
Bar-Or A, Pender MP, Khanna R, et al. Epstein-barr virus in multiple sclerosis: Theory and emerging immunotherapies. Trends Mol Med 2020; 26(3): 296-310.
[http://dx.doi.org/10.1016/j.molmed.2019.11.003] [PMID: 31862243]
[76]
Pender MP, Burrows SR. Epstein-Barr virus and multiple sclerosis: Potential opportunities for immunotherapy. Clin Transl Immunology 2014; 3(10): e27.
[http://dx.doi.org/10.1038/cti.2014.25] [PMID: 25505955]
[77]
Forte E, Luftig MA. The role of microRNAs in Epstein-Barr virus latency and lytic reactivation. Microbes Infect 2011; 13(14-15): 1156-67.
[http://dx.doi.org/10.1016/j.micinf.2011.07.007] [PMID: 21835261]
[78]
Hassani A, Khan G. Epstein-barr virus and miRNAs: Partners in crime in the pathogenesis of multiple sclerosis? Front Immunol 2019; 10: 695.
[http://dx.doi.org/10.3389/fimmu.2019.00695] [PMID: 31001286]
[79]
Rosato P, Anastasiadou E, Garg N, et al. Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2. Leukemia 2012; 26(11): 2343-52.
[http://dx.doi.org/10.1038/leu.2012.108] [PMID: 22614176]
[80]
Peedicayil J. Epigenetic drugs for multiple sclerosis. Curr Neuropharmacol 2016; 14(1): 3-9.
[http://dx.doi.org/10.2174/1570159X13666150211001600] [PMID: 26813117]
[81]
Banik D, Moufarrij S, Villagra A. Immunoepigenetics combination therapies: An overview of the role of HDACs in cancer immunotherapy. Int J Mol Sci 2019; 20(9): 20.
[http://dx.doi.org/10.3390/ijms20092241] [PMID: 31067680]
[82]
Castro K, Casaccia P. Epigenetic modifications in brain and immune cells of multiple sclerosis patients. Mult Scler 2018; 24(1): 69-74.
[http://dx.doi.org/10.1177/1352458517737389] [PMID: 29307300]
[83]
Pinto-Medel MJ, Oliver-Martos B, Urbaneja-Romero P, et al. Global methylation correlates with clinical status in multiple sclerosis patients in the first year of IFNbeta treatment. Sci Rep 2017; 7(1): 8727.
[http://dx.doi.org/10.1038/s41598-017-09301-2] [PMID: 28821874]
[84]
Cox MB, Cairns MJ, Gandhi KS, et al. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One 2010; 5(8): e12132.
[http://dx.doi.org/10.1371/journal.pone.0012132] [PMID: 20711463]
[85]
Zhu E, Wang X, Zheng B, et al. miR-20b suppresses Th17 differentiation and the pathogenesis of experimental autoimmune encephalomyelitis by targeting RORγt and STAT3. J Immunol 2014; 192(12): 5599-609.
[http://dx.doi.org/10.4049/jimmunol.1303488] [PMID: 24842756]
[86]
Ingwersen J, Menge T, Wingerath B, et al. Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b. Ann Clin Transl Neurol 2015; 2(1): 43-55.
[http://dx.doi.org/10.1002/acn3.152] [PMID: 25642434]
[87]
Lorenzi JC, Brum DG, Zanette DL, et al. miR-15a and 16-1 are downregulated in CD4+ T cells of multiple sclerosis relapsing patients. Int J Neurosci 2012; 122(8): 466-71.
[http://dx.doi.org/10.3109/00207454.2012.678444] [PMID: 22463747]
[88]
Cruz LO, Hashemifar SS, Wu CJ, et al. Excessive expression of miR-27 impairs Treg-mediated immunological tolerance. J Clin Invest 2017; 127(2): 530-42.
[http://dx.doi.org/10.1172/JCI88415] [PMID: 28067667]
[89]
Naghavian R, Ghaedi K, Kiani-Esfahani A, Ganjalikhani-Hakemi M, Etemadifar M, Nasr-Esfahani MH. miR-141 and miR-200a, revelation of new possible players in modulation of Th17/Treg differentiation and pathogenesis of multiple sclerosis. PLoS One 2015; 10(5): e0124555.
[http://dx.doi.org/10.1371/journal.pone.0124555] [PMID: 25938517]
[90]
Hu R, Huffaker TB, Kagele DA, et al. MicroRNA-155 confers encephalogenic potential to Th17 cells by promoting effector gene expression. J Immunol 2013; 190(12): 5972-80.
[http://dx.doi.org/10.4049/jimmunol.1300351] [PMID: 23686497]
[91]
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]
[92]
Ichiyama K, Gonzalez-Martin A, Kim BS, et al. The MicroRNA-183-96-182 cluster promotes T helper 17 cell pathogenicity by negatively regulating transcription factor foxo1 expression. Immunity 2016; 44(6): 1284-98.
[http://dx.doi.org/10.1016/j.immuni.2016.05.015] [PMID: 27332731]
[93]
Li Y, Singer NG, Whitbred J, Bowen MA, Fox DA, Lin F. CD6 as a potential target for treating multiple sclerosis. Proc Natl Acad Sci USA 2017; 114(10): 2687-92.
[http://dx.doi.org/10.1073/pnas.1615253114] [PMID: 28209777]
[94]
Restorick SM, Durant L, Kalra S, et al. CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells. Brain Behav Immun 2017; 64: 71-9.
[http://dx.doi.org/10.1016/j.bbi.2017.03.008] [PMID: 28336414]
[95]
Rossi S, Mancino R, Bergami A, et al. Potential role of IL-13 in neuroprotection and cortical excitability regulation in multiple sclerosis. Mult Scler 2011; 17(11): 1301-12.
[http://dx.doi.org/10.1177/1352458511410342] [PMID: 21677024]
[96]
Toghi M, Taheri M, Arsang-Jang S, et al. SOCS gene family expression profile in the blood of multiple sclerosis patients. J Neurol Sci 2017; 375: 481-5.
[http://dx.doi.org/10.1016/j.jns.2017.02.015] [PMID: 28196747]
[97]
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]
[98]
Lee PW, Severin ME, Lovett-Racke AE. TGF-β regulation of encephalitogenic and regulatory T cells in multiple sclerosis. Eur J Immunol 2017; 47(3): 446-53.
[http://dx.doi.org/10.1002/eji.201646716] [PMID: 28102541]
[99]
Donninelli G, Saraf-Sinik I, Mazziotti V, et al. Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain. J Neuroinflammation 2020; 17(1): 149.
[http://dx.doi.org/10.1186/s12974-020-01770-z] [PMID: 32375811]
[100]
Stilund M, Gjelstrup MC, Petersen T, Møller HJ, Rasmussen PV, Christensen T. Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel. PLoS One 2015; 10(4): e0119681.
[http://dx.doi.org/10.1371/journal.pone.0119681] [PMID: 25860354]
[101]
Tahani S, Dehghani L, Jahanbani-Ardakani H, et al. Elevated serum level of IL-4 in neuromyelitis optica and multiple sclerosis patients. J Immunoassay Immunochem 2019; 40(5): 555-63.
[http://dx.doi.org/10.1080/15321819.2019.1655649] [PMID: 31422745]
[102]
Capone A, Bianco M, Ruocco G, et al. Distinct expression of inflammatory features in T helper 17 cells from multiple sclerosis patients. Cells 2019; 8(6): 8.
[http://dx.doi.org/10.3390/cells8060533] [PMID: 31167379]
[103]
Guo B. IL-10 modulates Th17 pathogenicity during autoimmune diseases. J Clin Cell Immunol 2016; 7(2): 7.
[http://dx.doi.org/10.4172/2155-9899.1000400] [PMID: 27308096]
[104]
Göbel K, Ruck T, Meuth SG. Cytokine signaling in multiple sclerosis: Lost in translation. Mult Scler 2018; 24(4): 432-9.
[http://dx.doi.org/10.1177/1352458518763094] [PMID: 29512406]
[105]
Liu H, Rohowsky-Kochan C. Interleukin-27-mediated suppression of human Th17 cells is associated with activation of STAT1 and suppressor of cytokine signaling protein 1. J Interferon Cytokine Res 2011; 31(5): 459-69.
[http://dx.doi.org/10.1089/jir.2010.0115] [PMID: 21235411]
[106]
Ramgolam VS, Markovic-Plese S. Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets 2010; 10(2): 161-7.
[http://dx.doi.org/10.2174/187153010791213029] [PMID: 20384573]
[107]
Balasa R, Barcutean L, Balasa A, Motataianu A, Roman-Filip C, Manu D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum Immunol 2020; 81(5): 237-43.
[http://dx.doi.org/10.1016/j.humimm.2020.02.009] [PMID: 32122685]
[108]
Ghalamfarsa G, Mahmoudi M, Mohammadnia-Afrouzi M, et al. IL-21 and IL-21 receptor in the immunopathogenesis of multiple sclerosis. J Immunotoxicol 2016; 13(3): 274-85.
[http://dx.doi.org/10.3109/1547691X.2015.1089343] [PMID: 26507681]

© 2024 Bentham Science Publishers | Privacy Policy