{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:24:57Z","timestamp":1790709897666,"version":"4.1.0"},"reference-count":197,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"The Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["TO 977\/1-1"],"award-info":[{"award-number":["TO 977\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008722","name":"Universitat de Girona","doi-asserted-by":"publisher","award":["IFUdG2017"],"award-info":[{"award-number":["IFUdG2017"]}],"id":[{"id":"10.13039\/100008722","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system characterised by incoordination, sensory loss, weakness, changes in bladder capacity and bowel function, fatigue and cognitive impairment, creating a significant socioeconomic burden. The pathogenesis of MS involves both genetic susceptibility and exposure to distinct environmental risk factors. The gene x environment interaction is regulated by epigenetic mechanisms. Epigenetics refers to a complex system that modifies gene expression without altering the DNA sequence. The most studied epigenetic mechanism is DNA methylation. This epigenetic mark participates in distinct MS pathophysiological processes, including blood\u2013brain barrier breakdown, inflammatory response, demyelination, remyelination failure and neurodegeneration. In this study, we also accurately summarised a list of environmental factors involved in the MS pathogenesis and its clinical course. A literature search was conducted using MEDLINE through PubMED and Scopus. In conclusion, an exhaustive study of DNA methylation might contribute towards new pharmacological interventions in MS by use of epigenetic drugs.<\/jats:p>","DOI":"10.1186\/s12974-019-1667-1","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T10:02:40Z","timestamp":1578996160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients"],"prefix":"10.1186","volume":"17","author":[{"given":"Naiara","family":"Celarain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-3436","authenticated-orcid":false,"given":"Jordi","family":"Tomas-Roig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"1667_CR1","first-page":"1","volume":"19","author":"N Ghasemi","year":"2017","unstructured":"Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy citation. Cell J. 2017;19:1\u201310.","journal-title":"Cell J"},{"key":"1667_CR2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/archneur.58.1.65","volume":"58","author":"N De Stefano","year":"2001","unstructured":"De Stefano N, Narayanan S, Francis GS, Arnaoutelis R, Tartaglia MC, Antel JP, et al. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol. 2001;58:65\u201370.","journal-title":"Arch Neurol"},{"key":"1667_CR3","volume-title":"Seminar multiple sclerosis","author":"A Compston","year":"2008","unstructured":"Compston A, Coles A. Seminar multiple sclerosis; 2008."},{"key":"1667_CR4","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.euroneuro.2011.05.001","volume":"22","author":"P Jennum","year":"2012","unstructured":"Jennum P, Wanscher B, Frederiksen J, Kjellberg J. The socioeconomic consequences of multiple sclerosis: a controlled national study. Eur Neuropsychopharmacol. 2012;22:36\u201343. https:\/\/doi.org\/10.1016\/j.euroneuro.2011.05.001.","journal-title":"Eur Neuropsychopharmacol"},{"key":"1667_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jneuroim.2009.10.015","volume":"221","author":"R Gandhi","year":"2010","unstructured":"Gandhi R, Laroni A, Weiner HL. Role of the innate immune system in the pathogenesis of multiple sclerosis. J Neuroimmunol. 2010;221:7\u201314. https:\/\/doi.org\/10.1016\/j.jneuroim.2009.10.015.","journal-title":"J Neuroimmunol"},{"issue":"9","key":"1667_CR6","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1182\/blood-2008-02-139147","volume":"113","author":"Arne Sattler","year":"2009","unstructured":"Sattler A, Wagner U, Rossol M, Sieper J, Wu P, Krause A, et al. Cytokine-induced human IFN-\u03b3-secreting effector-memory Th cells in chronic autoimmune inflammation. Blood. 2009;113:1948\u201356.","journal-title":"Blood"},{"key":"1667_CR7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/jlb.58.4.373","volume":"58","author":"HA Young","year":"1995","unstructured":"Young HA, Hardy KJ. Role of interferon-\u03b3 in immune cell regulation. J Leukoc Biol. 1995;58:373\u201381.","journal-title":"J Leukoc Biol"},{"key":"1667_CR8","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/j.1600-065X.2012.01127.x","volume":"248","author":"Y Takeshita","year":"2012","unstructured":"Takeshita Y, Ransohoff RM. Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models. Immunol Rev. 2012;248:228\u201339.","journal-title":"Immunol Rev"},{"key":"1667_CR9","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.it.2015.08.006.Revisiting","volume":"36","author":"A Louveau","year":"2016","unstructured":"Louveau A, Harris TH, Kipnis J. Revisiting the concept of CNS immune privilege. Trends Immunol. 2016;36:569\u201377. https:\/\/doi.org\/10.1016\/j.it.2015.08.006.Revisiting.","journal-title":"Trends Immunol"},{"key":"1667_CR10","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1111\/j.1365-2990.2006.00781.x","volume":"33","author":"S Leech","year":"2007","unstructured":"Leech S, Kirk J, Plumb J, McQuaid S. Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis. Neuropathol Appl Neurobiol. 2007;33:86\u201398.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1667_CR11","doi-asserted-by":"publisher","first-page":"3770","DOI":"10.1016\/j.febslet.2011.04.066","volume":"585","author":"C Larochelle","year":"2011","unstructured":"Larochelle C, Alvarez JI, Prat A. How do immune cells overcome the blood-brain barrier in multiple sclerosis? FEBS Lett. 2011;585:3770\u201380. https:\/\/doi.org\/10.1016\/j.febslet.2011.04.066.","journal-title":"FEBS Lett"},{"key":"1667_CR12","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1126\/scitranslmed.aaa8038","volume":"7","author":"Y Cao","year":"2015","unstructured":"Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, et al. Distinct inflammatory profiles of myelin-reactive t cells from patients with multiple sclerosis HHS Public Access. Sci Transl Med. 2015;7:287\u201374. https:\/\/doi.org\/10.1126\/scitranslmed.aaa8038.","journal-title":"Sci Transl Med"},{"key":"1667_CR13","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0074-7742(07)79003-7","volume":"79","author":"T Chitnis","year":"2007","unstructured":"Chitnis T. The role of CD4 T cells in the pathogenesis of multiple sclerosis. Int Rev Neurobiol. 2007;79:43\u201372.","journal-title":"Int Rev Neurobiol"},{"key":"1667_CR14","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3389\/fneur.2015.00180","volume":"6","author":"J Correale","year":"2015","unstructured":"Correale J, Farez MF, Cardona AE. The role of astrocytes in multiple sclerosis progression. Front Neurol. 2015;6:180.","journal-title":"Front Neurol"},{"key":"1667_CR15","first-page":"96","volume":"3","author":"S Najafi","year":"2015","unstructured":"Najafi S, Mirshafiey A. The effect of activated microglia in progression of multiple sclerosis. Int Trends Immun. 2015;3:96\u2013104.","journal-title":"Int Trends Immun"},{"key":"1667_CR16","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1517\/14728222.2013.815726","volume":"17","author":"A Denic","year":"2013","unstructured":"Denic A, Wootla B, Rodriguez M. CD8 + T cells in multiple sclerosis. Expert Opin Ther Targets. 2013;17:1053\u201366.","journal-title":"Expert Opin Ther Targets"},{"key":"1667_CR17","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nrneurol.2012.203","volume":"8","author":"M Krumbholz","year":"2012","unstructured":"Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol. 2012;8:613\u201323. https:\/\/doi.org\/10.1038\/nrneurol.2012.203.","journal-title":"Nat Rev Neurol"},{"key":"1667_CR18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.cell.2018.08.011","volume":"175","author":"I Jelcic","year":"2018","unstructured":"Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R, Jelcic I, et al. Memory B cells activate brain-homing, autoreactive CD4+ T cells in multiple sclerosis. Cell. 2018;175:85\u2013100 e23.","journal-title":"Cell"},{"key":"1667_CR19","doi-asserted-by":"crossref","unstructured":"Stassart RM, M\u00f6bius W, Nave KA, Edgar JM. The axon-myelin unit in development and degenerative disease. Front Neurosci. 2018;12:467.","DOI":"10.3389\/fnins.2018.00467"},{"issue":"9","key":"1667_CR20","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1111\/j.1468-1331.2010.03003.x","volume":"17","author":"A. E. Handel","year":"2010","unstructured":"Handel AE, Handunnetthi L, Giovannoni G, Ebers GC, Ramagopalan S V. Genetic and environmental factors and the distribution of multiple sclerosis in Europe. Eur J Neurol. 2010;17:1210\u20134.","journal-title":"European Journal of Neurology"},{"key":"1667_CR21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1467-8624.2009.01381.x","volume":"81","author":"MJ Meaney","year":"2010","unstructured":"Meaney MJ. Epigenetics and the biological definition of gene X environment interactions. Child Dev. 2010;81:41\u201379.","journal-title":"Child Dev"},{"key":"1667_CR22","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/j.1600-065X.2012.01134.x","volume":"248","author":"PA Gourraud","year":"2012","unstructured":"Gourraud PA, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: an up-to-date review. Immunol Rev. 2012;248:87\u2013103.","journal-title":"Immunol Rev"},{"key":"1667_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fneur.2014.00130","volume":"5","author":"CM Lill","year":"2014","unstructured":"Lill CM. Recent advances and future challenges in the genetics of multiple sclerosis. Front Neurol. 2014;5:1\u20135.","journal-title":"Front Neurol"},{"key":"1667_CR24","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.21117","volume":"61","author":"A Ascherio","year":"2007","unstructured":"Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol. 2007;61:288\u201399.","journal-title":"Ann Neurol"},{"key":"1667_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-016-0001-8","volume":"6","author":"H Wu","year":"2016","unstructured":"Wu H, Huang X, Qiu H, Zhao M, Liao W, Yuan S, et al. High salt promotes autoimmunity by TET2-induced DNA demethylation and driving the differentiation of Tfh cells. Sci Rep. 2016;6:1\u201314.","journal-title":"Sci Rep"},{"key":"1667_CR26","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrg.2016.59","volume":"17","author":"CD Allis","year":"2016","unstructured":"Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17:487\u2013500. https:\/\/doi.org\/10.1038\/nrg.2016.59.","journal-title":"Nat Rev Genet"},{"key":"1667_CR27","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1093\/nar\/10.8.2709","volume":"10","author":"M Ehrlich","year":"1982","unstructured":"Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, Mccune RA, et al. Amount and distribution of 5-methylcytosine in human DNA from different types of tissues or cells. Nucleic Acids Res. 1982;10:2709\u201321.","journal-title":"Nucleic Acids Res"},{"key":"1667_CR28","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ng1990","volume":"39","author":"M Weber","year":"2007","unstructured":"Weber M, Hellmann I, Stadler MB, Ramos L, P\u00e4\u00e4bo S, Rebhan M, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39:457\u201366.","journal-title":"Nat Genet"},{"key":"1667_CR29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/B978-0-12-387685-0.00006-8","volume":"101","author":"\u017dM Svedru\u017ei\u0107","year":"2011","unstructured":"Svedru\u017ei\u0107 \u017dM. Dnmt1: Structure and function. Prog Mol Biol Transl Sci. 2011;101:221\u201354.","journal-title":"Prog Mol Biol Transl Sci"},{"key":"1667_CR30","doi-asserted-by":"publisher","first-page":"8905","DOI":"10.1073\/pnas.0501034102","volume":"102","author":"O Mortusewicz","year":"2005","unstructured":"Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H. Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci. 2005;102:8905\u20139. https:\/\/doi.org\/10.1073\/pnas.0501034102.","journal-title":"Proc Natl Acad Sci"},{"key":"1667_CR31","doi-asserted-by":"publisher","first-page":"4984","DOI":"10.1093\/nar\/gkr116","volume":"39","author":"BO Van Emburgh","year":"2011","unstructured":"Van Emburgh BO, Robertson KD. Modulation of Dnmt3b function in vitro by interactions with Dnmt3L, Dnmt3a and Dnmt3b splice variants. Nucleic Acids Res. 2011;39:4984\u20135002.","journal-title":"Nucleic Acids Res"},{"key":"1667_CR32","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/ng.946","volume":"43","author":"F Lienert","year":"2011","unstructured":"Lienert F, Wirbelauer C, Som I, Dean A, Mohn F, Sch\u00fcbeler D. Identification of genetic elements that autonomously determine DNA methylation states. Nat Genet. 2011;43:1091\u20137. https:\/\/doi.org\/10.1038\/ng.946.","journal-title":"Nat Genet"},{"key":"1667_CR33","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1093\/icb\/ict019","volume":"53","author":"KB Flores","year":"2013","unstructured":"Flores KB, Wolschin F, Amdam GV. The role of methylation of DNA in environmental adaptation. Integr Comp Biol. 2013;53:359\u201372.","journal-title":"Integr Comp Biol"},{"key":"1667_CR34","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1038\/emboj.2012.331","volume":"32","author":"S Kagiwada","year":"2013","unstructured":"Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M. Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J. 2013;32:340\u201353.","journal-title":"EMBO J"},{"key":"1667_CR35","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1038\/nature09303","volume":"466","author":"S Ito","year":"2010","unstructured":"Ito S, Dalessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. Role of tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature. 2010;466:1129\u201333. https:\/\/doi.org\/10.1038\/nature09303.","journal-title":"Nature"},{"key":"1667_CR36","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1126\/science.1210597","volume":"333","author":"S Ito","year":"2011","unstructured":"Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine. Science. 2011;333:1300\u20133.","journal-title":"Science"},{"key":"1667_CR37","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.cell.2011.03.022","volume":"145","author":"JU Guo","year":"2011","unstructured":"Guo JU, Su Y, Zhong C, Ming GL, Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell. 2011;145:423\u201334. https:\/\/doi.org\/10.1016\/j.cell.2011.03.022.","journal-title":"Cell"},{"key":"1667_CR38","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.cell.2011.06.020","volume":"146","author":"S Cortellino","year":"2011","unstructured":"Cortellino S, Xu J, Sannai M, Moore R, Caretti E, Cigliano A, et al. Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell. 2011;146:67\u201379.","journal-title":"Cell"},{"key":"1667_CR39","doi-asserted-by":"crossref","unstructured":"Maltby VE, Graves MC, Lea RA, Benton MC, Sanders KA, Tajouri L, et al. Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients. Clin Epigenetics. 2015;7:1\u20136. http:\/\/dx.doi.org\/10.1186\/s13148-015-0152-7","DOI":"10.1186\/s13148-015-0152-7"},{"issue":"8","key":"1667_CR40","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1177\/1352458513516529","volume":"20","author":"MC Graves","year":"2013","unstructured":"Graves MC, Benton M, Lea RA, Boyle M, Tajouri L, Macartney-Coxson D, et al. Methylation differences at the HLA-DRB1 locus in CD4+ T-cells are associated with multiple sclerosis. Mult Scler J. 2014;20:1033\u201341.","journal-title":"Multiple Sclerosis Journal"},{"key":"1667_CR41","doi-asserted-by":"crossref","unstructured":"Chomyk AM, Volsko C, Tripathi A, Deckard SA, Trapp BD, Fox RJ, et al. DNA methylation in demyelinated multiple sclerosis hippocampus. Sci Rep. 2017;7:1\u201310. http:\/\/dx.doi.org\/10.1038\/s41598-017-08623-5.","DOI":"10.1038\/s41598-017-08623-5"},{"key":"1667_CR42","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jneuroim.2015.11.018","volume":"290","author":"Paolo Fagone","year":"2016","unstructured":"Fagone P, Mangano K, di Marco R, Touil-Boukoffa C, Chikovan T, Signorelli S, et al. Expression of DNA methylation genes in secondary progressive multiple sclerosis. J Neuroimmunol. 2016;290:66\u20139.","journal-title":"Journal of Neuroimmunology"},{"key":"1667_CR43","doi-asserted-by":"publisher","first-page":"103","DOI":"10.32607\/20758251-2016-8-3-103-110","volume":"8","author":"OG Kulakova","year":"2016","unstructured":"Kulakova OG, Kabilov MR, Danilova LV, Popova EV, Baturina OA, Tsareva EY, et al. Whole-genome DNA methylation analysis of peripheral blood mononuclear cells in multiple sclerosis patients with different disease courses. Acta Naturae. 2016;8:103\u201310.","journal-title":"Acta Naturae"},{"key":"1667_CR44","doi-asserted-by":"crossref","unstructured":"Marabita F, Almgren M, Sj\u00f6holm LK, Kular L, Liu Y, James T, et al. Smoking induces DNA methylation changes in multiple sclerosis patients with exposure-response relationship. Sci Rep. 2017;7:1\u201315.","DOI":"10.1038\/s41598-017-14788-w"},{"key":"1667_CR45","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1002\/jnr.21329","volume":"85","author":"FG Mastronardi","year":"2007","unstructured":"Mastronardi FG, Noor A, Wood DD, Paton T, Moscarello MA. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res. 2007;85:2006\u201316.","journal-title":"J Neurosci Res"},{"issue":"13","key":"1667_CR46","doi-asserted-by":"publisher","first-page":"E1826","DOI":"10.1073\/pnas.1519286113","volume":"113","author":"Roni Lehmann-Werman","year":"2016","unstructured":"Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, et al. Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci. 2016;113:e1826\u201334. http:\/\/dx.doi.org\/10.1073\/pnas.1519286113.","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"1667_CR47","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nn.3588","volume":"17","author":"JL Huynh","year":"2014","unstructured":"Huynh JL, Garg P, Thin TH, Yoo S, Dutta R, Trapp BD, et al. Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci. 2014;17:121\u201330. https:\/\/doi.org\/10.1038\/nn.3588.","journal-title":"Nat Neurosci"},{"issue":"3","key":"1667_CR48","doi-asserted-by":"publisher","first-page":"e0117403","DOI":"10.1371\/journal.pone.0117403","volume":"10","author":"Steffan D. Bos","year":"2015","unstructured":"Bos SD, Page CM, Andreassen BK, Elboudwarej E, Gustavsen MW, Briggs F, et al. Genome-wide DNA methylation profiles indicate CD8+ T cell hypermethylation in multiple sclerosis. PLoS One. 2015;10:1\u201316.","journal-title":"PLOS ONE"},{"key":"1667_CR49","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jneuroim.2012.03.003","volume":"246","author":"C Kumagai","year":"2012","unstructured":"Kumagai C, Kalman B, Middleton FA, Vyshkina T, Massa PT. Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. J Neuroimmunol. 2012;246:51\u20137. https:\/\/doi.org\/10.1016\/j.jneuroim.2012.03.003.","journal-title":"J Neuroimmunol"},{"issue":"2","key":"1667_CR50","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/gene.2016.50","volume":"18","author":"J Field","year":"2017","unstructured":"Field J, Fox A, Jordan MA, Baxter AG, Spelman T, Gresle M, et al. Interleukin-2 receptor-\u03b1 proximal promoter hypomethylation is associated with multiple sclerosis. Genes Immun. 2017;18:59\u201366. http:\/\/dx.doi.org\/10.1038\/gene.2016.50.","journal-title":"Genes & Immunity"},{"key":"1667_CR51","doi-asserted-by":"crossref","unstructured":"Pinto-Medel MJ, Oliver-Martos B, Urbaneja-Romero P, Hurtado-Guerrero I, Ortega-Pinazo J, Serrano-Castro 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\u20139.","DOI":"10.1038\/s41598-017-09301-2"},{"key":"1667_CR52","doi-asserted-by":"crossref","unstructured":"Baranzini SE, Mudge J, Van Velkinburgh JC, Khankhanian P, Khrebtukova I, Miller NA, et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature. 2010;464:1351\u20136. http:\/\/dx.doi.org\/10.1038\/nature08990.","DOI":"10.1038\/nature08990"},{"key":"1667_CR53","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.ebiom.2016.06.031","volume":"10","author":"John A. Olsen","year":"2016","unstructured":"Olsen JA, Kenna LA, Tipon RC, Spelios MG, Stecker MM, Akirav EM. A minimally-invasive blood-derived biomarker of oligodendrocyte cell-loss in multiple sclerosis. EBioMedicine. 2016;10:227\u201335.","journal-title":"EBioMedicine"},{"issue":"6","key":"1667_CR54","doi-asserted-by":"publisher","first-page":"4681","DOI":"10.1007\/s12035-017-0679-z","volume":"55","author":"Marina Dunaeva","year":"2017","unstructured":"Dunaeva M, Derksen M, Pruijn GJM. LINE-1 Hypermethylation in serum cell-free DNA of relapsing remitting multiple sclerosis patients. Mol Neurobiol. 2018;55:4681\u20138.","journal-title":"Molecular Neurobiology"},{"issue":"3","key":"1667_CR55","doi-asserted-by":"publisher","first-page":"e0174726","DOI":"10.1371\/journal.pone.0174726","volume":"12","author":"Teresa Ayuso","year":"2017","unstructured":"Ayuso T, Aznar P, Soriano L, Olaskoaga A, Rold\u00e1n M, Otano M, et al. Vitamin D receptor gene is epigenetically altered and transcriptionally up-regulated in multiple sclerosis. PLoS One. 2017;12:1\u201310.","journal-title":"PLOS ONE"},{"key":"1667_CR56","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jns.2009.12.018","volume":"290","author":"T Liggett","year":"2010","unstructured":"Liggett T, Melnikov A, Tilwalli S, Yi Q, Chen H, Replogle C, et al. Methylation patterns of cell-free plasma DNA in relapsing-remitting multiple sclerosis. J Neurol Sci. 2010;290:16\u201321. https:\/\/doi.org\/10.1016\/j.jns.2009.12.018.","journal-title":"J Neurol Sci"},{"key":"1667_CR57","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1007\/s12031-018-1046-x","volume":"64","author":"M Sokratous","year":"2018","unstructured":"Sokratous M, Dardiotis E, Bellou E, Tsouris Z, Michalopoulou A, Dardioti M, et al. CpG island methylation patterns in relapsing-remitting multiple sclerosis. J Mol Neurosci. 2018;64:478\u201384.","journal-title":"J Mol Neurosci"},{"key":"1667_CR58","doi-asserted-by":"crossref","unstructured":"Souren NY, Gerdes LA, Lutsik P, Gasparoni G, Beltran E, Salhab A, et al. DNA methylation signatures of a large cohort monozygotic twins clinically discordant for multiple sclerosis; 2018. http:\/\/dx.doi.org\/10.1101\/381822.","DOI":"10.1101\/381822"},{"key":"1667_CR59","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1177\/1352458511421055","volume":"18","author":"R Calabrese","year":"2012","unstructured":"Calabrese R, Zampieri M, Mechelli R, Annibali V, Guastafierro T, Ciccarone F, et al. Methylation-dependent PAD2 upregulation in multiple sclerosis peripheral blood. Mult Scler J. 2012;18:299\u2013304.","journal-title":"Mult Scler J"},{"issue":"7","key":"1667_CR60","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.bbadis.2014.04.010","volume":"1842","author":"R. Calabrese","year":"2014","unstructured":"Calabrese R, Valentini E, Ciccarone F, Guastafierro T, Bacalini MG, Ricigliano VAG, et al. TET2 gene expression and 5-hydroxymethylcytosine level in multiple sclerosis peripheral blood cells. Biochim Biophys Acta - Mol Basis Dis. 1842;2014:1130\u20136.","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"issue":"10","key":"1667_CR61","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1177\/1352458517721356","volume":"24","author":"Sabrina Ruhrmann","year":"2017","unstructured":"Ruhrmann S, Ewing E, Piket E, Kular L, Cetrulo Lorenzi JC, Fernandes SJ, et al. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsingremitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes. Mult Scler J. 2017;24:1288\u20131300.","journal-title":"Multiple Sclerosis Journal"},{"key":"1667_CR62","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2174\/1567202043480152","volume":"1","author":"B Hemmer","year":"2004","unstructured":"Hemmer B, Cepok S, Zhou D, Sommer N. Multiple sclerosis -- a coordinated immune attack across the blood brain barrier 2. Curr Neurovasc Res. 2004;1:141\u201350. https:\/\/doi.org\/10.2174\/1567202043480152.","journal-title":"Curr Neurovasc Res"},{"key":"1667_CR63","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1021\/mp400624v","volume":"11","author":"NH On","year":"2014","unstructured":"On NH, Kiptoo P, Siahaan TJ, Miller DW. Modulation of blood-brain barrier permeability in mice using synthetic E-cadherin peptide. Mol Pharm. 2014;11:974\u201381.","journal-title":"Mol Pharm"},{"key":"1667_CR64","volume-title":"Cell adhesion molecules: implications in neurological diseases","author":"ML Montesinos","year":"2014","unstructured":"Montesinos ML. Cell adhesion molecules: implications in neurological diseases; 2014."},{"key":"1667_CR65","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/j.1365-2990.2010.01140.x","volume":"37","author":"J Greenwood","year":"2011","unstructured":"Greenwood J, Heasman SJ, Alvarez JI, Prat A, Lyck R, Engelhardt B. Review: Leucocyte-endothelial cell crosstalk at the blood-brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol Appl Neurobiol. 2011;37:24\u201339.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1667_CR66","doi-asserted-by":"publisher","first-page":"851","DOI":"10.4049\/jimmunol.178.2.851","volume":"178","author":"DC Bullard","year":"2007","unstructured":"Bullard DC, Hu X, Schoeb TR, Collins RG, Beaudet AL, Barnum SR. Intercellular adhesion molecule-1 expression is required on multiple cell types for the development of experimental autoimmune encephalomyelitis. J Immunol. 2007;178:851\u20137. https:\/\/doi.org\/10.4049\/jimmunol.178.2.851.","journal-title":"J Immunol"},{"key":"1667_CR67","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1016\/j.immuni.2017.06.002","volume":"46","author":"CL Dulberger","year":"2017","unstructured":"Dulberger CL, McMurtrey CP, H\u00f6lzemer A, Neu KE, Liu V, Steinbach AM, et al. Human leukocyte antigen F presents peptides and regulates immunity through interactions with NK cell receptors. Immunity. 2017;46:1018\u201329 e7.","journal-title":"Immunity"},{"issue":"2","key":"1667_CR68","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1093\/ndt\/16.2.355","volume":"16","author":"Christoph Frohn","year":"2001","unstructured":"Frohn C, Fricke L, Puchta JC, Kirchner H. The effect of HLA-C matching on acute renal transplant rejection. Nephrol Dial Transplant. 2001;16:355\u201360.","journal-title":"Nephrology Dialysis Transplantation"},{"key":"1667_CR69","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1084\/jem.20060028","volume":"203","author":"B Meresse","year":"2006","unstructured":"Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, et al. Reprogramming of CTLs into natural killer\u2013like cells in celiac disease. J Exp Med. 2006;203:1343\u201355. https:\/\/doi.org\/10.1084\/jem.20060028.","journal-title":"J Exp Med"},{"key":"1667_CR70","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/0896-6273(94)90211-9","volume":"12","author":"Y Yoshihara","year":"1994","unstructured":"Yoshihara Y, Oka S, Nemoto Y, Watanabe Y, Nagata S, Kagamiyama H, et al. An ICAM-related neuronal glycoprotein, telencephalin, with brain segment-specific expression. Neuron. 1994;12:541\u201353.","journal-title":"Neuron"},{"key":"1667_CR71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnmol.2017.00431","volume":"10","author":"S Paetau","year":"2017","unstructured":"Paetau S, Rolova T, Ning L, Gahmberg CG. Neuronal ICAM-5 inhibits microglia adhesion and phagocytosis and promotes an anti-inflammatory response in LPS stimulated microglia. Front Mol Neurosci. 2017;10:1\u201312. https:\/\/doi.org\/10.3389\/fnmol.2017.00431.","journal-title":"Front Mol Neurosci"},{"key":"1667_CR72","doi-asserted-by":"crossref","unstructured":"Lubetzki C, Stankoff B. Demyelination in multiple sclerosis. Handb Clin Neurol. 2014;122:89\u201399. http:\/\/sci-hub.tw\/10.1016\/B978-0-444-52001-2.00004-2.","DOI":"10.1016\/B978-0-444-52001-2.00004-2"},{"key":"1667_CR73","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1084\/jem.180.6.2227","volume":"180","author":"N Karin","year":"2004","unstructured":"Karin N. Reversal of experimental autoimmune encephalomyelitis by a soluble peptide variant of a myelin basic protein epitope: T cell receptor antagonism and reduction of interferon gamma and tumor necrosis factor alpha production. J Exp Med. 2004;180:2227\u201337.","journal-title":"J Exp Med"},{"key":"1667_CR74","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1084\/jem.191.8.1395","volume":"191","author":"M Krogsgaard","year":"2000","unstructured":"Krogsgaard M, Wucherpfennig KW, Cannella B, Hansen BE, Svejgaard A, Pyrdol J, et al. Visualization of myelin basic protein (Mbp) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (Hla)-Dr2\u2013Mbp 85\u201399 complex. J Exp Med. 2000;191:1395\u2013412.","journal-title":"J Exp Med"},{"key":"1667_CR75","doi-asserted-by":"publisher","unstructured":"Falc\u00e3o AM, Meijer M, Scaglione A, Rinwa P, Agirre E, Liang J, et al. PADI2-mediated citrullination is required for efficient oligodendrocyte differentiation and myelination. bioRxiv. 2018. https:\/\/doi.org\/10.1101\/425348.","DOI":"10.1101\/425348"},{"key":"1667_CR76","doi-asserted-by":"publisher","first-page":"5382","DOI":"10.1021\/bi9925571","volume":"39","author":"LB Pritzker","year":"2000","unstructured":"Pritzker LB, Joshi S, Harauz G, Moscarello MA. Deimination of myelin basic protein. 2. Effect of methylation of MBP on its deimination by peptidylarginine deiminase. Biochemistry. 2000;39:5382\u20138.","journal-title":"Biochemistry"},{"key":"1667_CR77","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/ana.410400106","volume":"40","author":"DD Wood","year":"1996","unstructured":"Wood DD, Bilbao JM, O\u2019Connors P, Moscarello MA. Acute multiple sclerosis (Marburg type) is associated with developmentally immature myelin basic protein. Ann Neurol. 1996;40:18\u201324.","journal-title":"Ann Neurol"},{"key":"1667_CR78","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/j.0105-2896.2005.00312.x","volume":"207","author":"C Watts","year":"2005","unstructured":"Watts C, Matthews SP, Mazzeo D, Manoury B, Moss CX. Asparaginyl endopeptidase: case history of a class II MHC compartment protease. Immunol Rev. 2005;207:218\u201328.","journal-title":"Immunol Rev"},{"key":"1667_CR79","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/ni754","volume":"3","author":"B Manoury","year":"2002","unstructured":"Manoury B, Mazzeo D, Fugger L, Viner N, Ponsford M, Streeter H, et al. Destructive processing by asparagine endopeptidase limits presentation of a dominant T cell epitope in MBP. Nat Immunol. 2002;3:169\u201374.","journal-title":"Nat Immunol"},{"key":"1667_CR80","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1523\/JNEUROSCI.18-02-00601.1998","volume":"18","author":"G Wolswijk","year":"1998","unstructured":"Wolswijk G. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci. 1998;18:601\u20139. https:\/\/doi.org\/10.1523\/JNEUROSCI.18-02-00601.1998.","journal-title":"J Neurosci"},{"key":"1667_CR81","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/nrn917","volume":"3","author":"RJM Franklin","year":"2002","unstructured":"Franklin RJM. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci. 2002;3:705\u201314.","journal-title":"Nat Rev Neurosci"},{"key":"1667_CR82","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1093\/brain\/awn096","volume":"131","author":"T Kuhlmann","year":"2008","unstructured":"Kuhlmann T, Miron V, Cuo Q, Wegner C, Antel J, Br\u00fcck W. Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain. 2008;131:1749\u201358.","journal-title":"Brain"},{"key":"1667_CR83","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1002\/(SICI)1097-4695(19981115)37:3<413::AID-NEU7>3.0.CO;2-8","volume":"37","author":"JM Redwine","year":"1998","unstructured":"Redwine JM, Armstrong RC. In vivo proliferation of oligodendrocyte progenitors expressing PDGF\u03b1R during early remyelination. J Neurobiol. 1998;37:413\u201328.","journal-title":"J Neurobiol"},{"key":"1667_CR84","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1006\/mcne.1999.0771","volume":"14","author":"GL Hinks","year":"1999","unstructured":"Hinks GL, Franklin RJM. Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-\u03b21 gene expression during remyelination of experimentally-induced spinal cord demyelination. Mol Cell Neurosci. 1999;14:153\u201368.","journal-title":"Mol Cell Neurosci"},{"key":"1667_CR85","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/1097-4547(20001015)62:2<241::AID-JNR9>3.0.CO;2-D","volume":"62","author":"DJ Messersmith","year":"2000","unstructured":"Messersmith DJ, Murtie JC, Le TQ, Frost EE, Armstrong RC. Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination. J Neurosci Res. 2000;62:241\u201356.","journal-title":"J Neurosci Res"},{"key":"1667_CR86","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1101\/gad.1806309","volume":"23","author":"SPJ Fancy","year":"2009","unstructured":"Fancy SPJ, Baranzini SE, Zhao C, Yuk D-I, Irvine K-A, Kaing S, et al. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev. 2009;23:1571\u201385.","journal-title":"Genes Dev"},{"key":"1667_CR87","doi-asserted-by":"publisher","first-page":"3027","DOI":"10.1242\/dev.01881","volume":"132","author":"M Yamaguchi","year":"2005","unstructured":"Yamaguchi M. Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development. 2005;132:3027\u201343. https:\/\/doi.org\/10.1242\/dev.01881.","journal-title":"Development"},{"key":"1667_CR88","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.cell.2004.11.051","volume":"120","author":"A Yamamoto","year":"2005","unstructured":"Yamamoto A, Nagano T, Takehara S, Hibi M, Aizawa S. Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF. Cell. 2005;120:223\u201335.","journal-title":"Cell"},{"key":"1667_CR89","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nn.2780","volume":"14","author":"Y Chen","year":"2011","unstructured":"Chen Y, Wang H, Yoon SO, Xu X, Hottiger MO, Svaren J, et al. HDAC-mediated deacetylation of NF-\u03baB is critical for Schwann cell myelination. Nat Neurosci. 2011;14:437\u201341.","journal-title":"Nat Neurosci"},{"key":"1667_CR90","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/S0896-6273(01)00294-X","volume":"30","author":"MA Bhat","year":"2001","unstructured":"Bhat MA, Rios JC, Lu Y, Garcia-Fresco GP, Ching W, Martin MS, et al. Axon-glia interactions and the domain organization of myelinated axons requires Neurexin IV\/Caspr\/Paranodin. Neuron. 2001;30:369\u201383.","journal-title":"Neuron"},{"key":"1667_CR91","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.neuron.2005.10.019","volume":"48","author":"DL Sherman","year":"2005","unstructured":"Sherman DL, Tait S, Melrose S, Johnson R, Zonta B, Court FA, et al. Neurofascins are required to establish axonal domains for saltatory conduction. Neuron. 2005;48:737\u201342.","journal-title":"Neuron"},{"key":"1667_CR92","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1084\/jem.20071053","volume":"204","author":"EK Mathey","year":"2007","unstructured":"Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007;204:2363\u201372. https:\/\/doi.org\/10.1084\/jem.20071053.","journal-title":"J Exp Med"},{"key":"1667_CR93","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0165-5728(92)90136-9","volume":"40","author":"C Linington","year":"1992","unstructured":"Linington C, Engelhardt B, Kapocs G, Lassman H. Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody. J Neuroimmunol. 1992;40:219\u201324.","journal-title":"J Neuroimmunol"},{"issue":"3","key":"1667_CR94","doi-asserted-by":"publisher","first-page":"a001271","DOI":"10.1101\/cshperspect.a001271","volume":"1","author":"B. Kaltschmidt","year":"2009","unstructured":"Kaltschmidt B, Kaltschmidt C. NF- kB in the nervous system. Cold Spring Harb Perspect Biol. 2009;1:a001271.","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"1667_CR95","doi-asserted-by":"crossref","unstructured":"Akama KT, Albanese C, Pestell RG, Van Eldik L. Amyloid beta-peptide stimulates nitric oxide production in astrocytes through an NFkappaB-dependent mechanism. Proc Natl Acad Sci U S A. 1998;95:5795\u2013800.","DOI":"10.1073\/pnas.95.10.5795"},{"key":"1667_CR96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13073-014-0060-z","volume":"6","author":"JE Castillo-Fernandez","year":"2014","unstructured":"Castillo-Fernandez JE, Spector TD, Bell JT. Epigenetics of discordant monozygotic twins: Implications for disease. Genome Med. 2014;6:1\u201316.","journal-title":"Genome Med"},{"key":"1667_CR97","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1001\/archneurol.2009.122","volume":"66","author":"BC Healy","year":"2009","unstructured":"Healy BC, Ali EN, Guttmann CRG, Chitnis T, Glanz BI, Buckle G, et al. Smoking and disease progression in multiple sclerosis. Arch Neurol. 2009;66:858\u201364.","journal-title":"Arch Neurol"},{"key":"1667_CR98","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.msard.2017.07.020","volume":"17","author":"ML Degelman","year":"2017","unstructured":"Degelman ML, Herman KM. Smoking and multiple sclerosis: a systematic review and meta-analysis using the Bradford Hill criteria for causation. Mult Scler Relat Disord. 2017;17:207\u201316.","journal-title":"Mult Scler Relat Disord"},{"key":"1667_CR99","doi-asserted-by":"publisher","first-page":"613","DOI":"10.3390\/ijerph8020613","volume":"8","author":"R Talhout","year":"2011","unstructured":"Talhout R, Schulz T, Florek E, van Benthem J, Wester P, Opperhuizen A. Hazardous compounds in tobacco smoke. Int J Environ Res Public Health. 2011;8:613\u201328.","journal-title":"Int J Environ Res Public Health"},{"key":"1667_CR100","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.brainres.2004.08.043","volume":"1027","author":"BT Hawkins","year":"2004","unstructured":"Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, Campos CR, et al. Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res. 2004;1027:48\u201358.","journal-title":"Brain Res"},{"key":"1667_CR101","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1191\/1352458503ms965oa","volume":"9","author":"A Minagar","year":"2003","unstructured":"Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Multiple Sclerosis. 2003;9:540\u20139.","journal-title":"Multiple Sclerosis"},{"key":"1667_CR102","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/BF00695572","volume":"64","author":"N Funata","year":"1984","unstructured":"Funata N, Song SY, Okeda R, Funata M, Higashino F. A study of experimental cyanide encephalopathy in the acute phase -physiological and neuropathological correlation. Acta Neuropathol. 1984;64:99\u2013107.","journal-title":"Acta Neuropathol"},{"key":"1667_CR103","doi-asserted-by":"crossref","unstructured":"Wang L, Hagemann TL, Kalwa H, Michel T, Messing A, Feany MB. Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nat Commun. 2015;6:8966.","DOI":"10.1038\/ncomms9966"},{"key":"1667_CR104","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.canlet.2006.11.015","volume":"252","author":"M Kitamura","year":"2007","unstructured":"Kitamura M, Kasai A. Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway. Cancer Lett. 2007;252:184\u201394.","journal-title":"Cancer Lett"},{"key":"1667_CR105","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s00281-013-0397-1","volume":"35","author":"FJ Quintana","year":"2013","unstructured":"Quintana FJ. Regulation of central nervous system autoimmunity by the aryl hydrocarbon receptor. Semin Immunopathol. 2013;35:627\u201335.","journal-title":"Semin Immunopathol"},{"issue":"7191","key":"1667_CR106","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature06880","volume":"453","author":"Francisco J. Quintana","year":"2008","unstructured":"Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, et al. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008;453:65\u201371.","journal-title":"Nature"},{"issue":"5","key":"1667_CR107","doi-asserted-by":"publisher","first-page":"e63812","DOI":"10.1371\/journal.pone.0063812","volume":"8","author":"Sonja Zeilinger","year":"2013","unstructured":"Zeilinger S, K\u00fchnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One. 2013;8:e63812.","journal-title":"PLoS ONE"},{"issue":"12","key":"1667_CR108","doi-asserted-by":"publisher","first-page":"3851","DOI":"10.3390\/ijms19123851","volume":"19","author":"Drew Neavin","year":"2018","unstructured":"Neavin DR, Liu D, Ray B, Weinshilboum RM. The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. Int J Mol Sci. 2018;19(12):3851.","journal-title":"International Journal of Molecular Sciences"},{"key":"1667_CR109","doi-asserted-by":"publisher","first-page":"e79819","DOI":"10.1371\/journal.pone.0079819","volume":"8","author":"JH Duarte","year":"2013","unstructured":"Duarte JH, Di Meglio P, Hirota K, Ahlfors H, Stockinger B. Differential influences of the aryl hydrocarbon receptor on Th17 mediated responses in vitro and in vivo. PLoS One. 2013;8:e79819.","journal-title":"PLoS One"},{"key":"1667_CR110","doi-asserted-by":"publisher","first-page":"9794","DOI":"10.1038\/s41598-017-09621-3","volume":"7","author":"L Juricek","year":"2017","unstructured":"Juricek L, Carcaud J, Pelhaitre A, Riday TT, Chevallier A, Lanzini J, et al. AhR-deficiency as a cause of demyelinating disease and inflammation. Sci Rep. 2017;7:9794.","journal-title":"Sci Rep"},{"key":"1667_CR111","doi-asserted-by":"publisher","first-page":"e359","DOI":"10.1212\/NXI.0000000000000359","volume":"4","author":"V Rothhammer","year":"2017","unstructured":"Rothhammer V, Borucki DM, Garcia Sanchez MI, Mazzola MA, Hemond CC, Regev K, et al. Dynamic regulation of serum aryl hydrocarbon receptor agonists in MS. Neurol Neuroimmunol Neuroinflamm. 2017;4:e359.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"1667_CR112","doi-asserted-by":"publisher","first-page":"e6145","DOI":"10.1073\/pnas.1607843113","volume":"113","author":"J Kaye","year":"2016","unstructured":"Kaye J, Piryatinsky V, Birnberg T, Hingaly T, Raymond E, Kashi R, et al. Laquinimod arrests experimental autoimmune encephalomyelitis by activating the aryl hydrocarbon receptor. Proc Natl Acad Sci. 2016;113:e6145\u201352. https:\/\/doi.org\/10.1073\/pnas.1607843113.","journal-title":"Proc Natl Acad Sci"},{"key":"1667_CR113","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s12026-014-8496-1","volume":"58","author":"OL Hatton","year":"2014","unstructured":"Hatton OL, Harris-Arnold A, Schaffert S, Krams SM, Martinez OM. The interplay between Epstein-Barr virus and B lymphocytes: implications for infection, immunity, and disease. Immunol Res. 2014;58:268\u201376.","journal-title":"Immunol Res"},{"key":"1667_CR114","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1001\/jama.286.24.3083","volume":"286","author":"A Ascherio","year":"2001","unstructured":"Ascherio A, Munger KL, Lennette ET, Spiegelman D, Hern\u00e1n MA, Olek MJ, et al. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. J Am Med Assoc. 2001;286:3083\u20138.","journal-title":"J Am Med Assoc."},{"key":"1667_CR115","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/nrneurol.2016.187","volume":"13","author":"T Olsson","year":"2017","unstructured":"Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017;13:25\u201336.","journal-title":"Nat Rev Neurol"},{"key":"1667_CR116","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1080\/08916930802024772","volume":"41","author":"HH Niller","year":"2008","unstructured":"Niller HH, Wolf H, Minarovits J. Regulation and dysregulation of Epstein - Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity. 2008;41:298\u2013328.","journal-title":"Autoimmunity"},{"issue":"5","key":"1667_CR117","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1172\/JCI200523661","volume":"115","author":"Sabine Cepok","year":"2005","unstructured":"Cepok S, Zhou D, Srivastava R, Nessler S, Stei S, B\u00fcssow K, et al. Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J Clin Invest. 2005;115:1352-60.","journal-title":"Journal of Clinical Investigation"},{"key":"1667_CR118","doi-asserted-by":"publisher","first-page":"6150","DOI":"10.1128\/MCB.15.11.6150","volume":"15","author":"KD Robertson","year":"1995","unstructured":"Robertson KD, Hayward SD, Ling PD, Samid D, Robertson KD, Hayward SD, et al. Transcriptional activation of the Epstein-Barr virus latency C promoter after 5-azacytidine treatment: evidence that demethylation at a single CpG site is crucial. Mol Cell Biol. 1995;15:6150\u20139.","journal-title":"Mol Cell Biol"},{"issue":"5","key":"1667_CR119","doi-asserted-by":"publisher","first-page":"482","DOI":"10.3390\/nu2050482","volume":"2","author":"Ola Engelsen","year":"2010","unstructured":"Engelsen O. The relationship between ultraviolet radiation exposure and vitamin D status. Nutrients. 2010;2:482\u2013495.","journal-title":"Nutrients"},{"issue":"6","key":"1667_CR120","doi-asserted-by":"publisher","first-page":"1678S","DOI":"10.1093\/ajcn\/80.6.1678S","volume":"80","author":"Michael F Holick","year":"2004","unstructured":"Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease... Vitamin D and Health in the 21st Century: proceedings of a conference held in Bethesda, MD, October 9-10, 2003. Am J Clin Nutr. 2004;80:1678S.","journal-title":"The American Journal of Clinical Nutrition"},{"issue":"1-2","key":"1667_CR121","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jneuroim.2007.11.014","volume":"194","author":"Joost Smolders","year":"2008","unstructured":"Smolders J, Damoiseaux J, Menheere P, Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol. 2008;194:7\u201317.","journal-title":"Journal of Neuroimmunology"},{"issue":"1","key":"1667_CR122","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1017\/S0317167100011124","volume":"38","author":"Scott Sloka","year":"2011","unstructured":"Sloka S, Silva C, Pryse-Phillips W, Patten S, Metz L, Yong VW. A quantitative analysis of suspected environmental causes of MS. Can J Neurol Sci. 2011;38:98\u2013105.","journal-title":"Canadian Journal of Neurological Sciences \/ Journal Canadien des Sciences Neurologiques"},{"key":"1667_CR123","doi-asserted-by":"crossref","unstructured":"Simpson S, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68:193\u2013203.","DOI":"10.1002\/ana.22043"},{"key":"1667_CR124","doi-asserted-by":"crossref","unstructured":"Fetahu IS, H\u00f6baus J, K\u00e1llay E. Vitamin D and the epigenome. Front Physiol. 2014;5:1\u201313.","DOI":"10.3389\/fphys.2014.00164"},{"issue":"7","key":"1667_CR125","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1080\/01635581.2012.711418","volume":"64","author":"James B. Rawson","year":"2012","unstructured":"Rawson JB, Sun Z, Dicks E, Daftary D, Parfrey PS, Green RC, et al. Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients. Nutr Cancer. 2012;64:919\u201328.","journal-title":"Nutrition and Cancer"},{"issue":"1","key":"1667_CR126","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s00441-014-1996-4","volume":"359","author":"Nibaldo C. Inestrosa","year":"2014","unstructured":"Inestrosa NC, Varela-Nallar L. Wnt signalling in neuronal differentiation and development. Cell Tissue Res. 2015;359:215\u201323.","journal-title":"Cell and Tissue Research"},{"issue":"12","key":"1667_CR127","doi-asserted-by":"publisher","first-page":"e51506","DOI":"10.1371\/journal.pone.0051506","volume":"7","author":"Carolina Barrag\u00e1n-Mart\u00ednez","year":"2012","unstructured":"Barrag\u00e1n-Mart\u00ednez C, Speck-Hern\u00e1ndez CA, Montoya-Ortiz G, Mantilla RD, Anaya JM, Rojas-Villarraga A, et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS One. 2012;7:e51506.","journal-title":"PLoS ONE"},{"key":"1667_CR128","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00401-010-0653-6","volume":"119","author":"Z Al-Hajri","year":"2010","unstructured":"Al-Hajri Z, Del Bigio MR. Brain damage in a large cohort of solvent abusers. Acta Neuropathol. 2010;119:435\u201345.","journal-title":"Acta Neuropathol"},{"key":"1667_CR129","doi-asserted-by":"publisher","first-page":"269","DOI":"10.2217\/epi.12.23","volume":"4","author":"L Godderis","year":"2012","unstructured":"Godderis L, De Raedt K, Tabish AM, Poels K, Maertens N, De Ruyck K, et al. Epigenetic changes in lymphocytes of solvent-exposed individuals. Epigenomics. 2012;4:269\u201377.","journal-title":"Epigenomics"},{"key":"1667_CR130","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.envres.2015.12.014","volume":"146","author":"Ji Young Hong","year":"2016","unstructured":"Hong JY, Yu SY, Kim SY, Ahn JJ, Kim Y, Kim GW, et al. Association analysis of toluene exposure time with high-throughput mRNA expressions and methylation patterns using in vivo samples. Environ Res. 2016;146:59\u201364.","journal-title":"Environmental Research"},{"key":"1667_CR131","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1074\/jbc.273.1.528","volume":"273","author":"C Wu","year":"1998","unstructured":"Wu C, Keightley SY, Leung-Hagesteijn C, Radeva G, Coppolino M, Goicoechea S, et al. Integrin-linked protein kinase regulates fibronectin matrix assembly, E- cadherin expression, and tumorigenicity. J Biol Chem. 1998;273:528\u201336.","journal-title":"J Biol Chem"},{"key":"1667_CR132","doi-asserted-by":"publisher","first-page":"e455","DOI":"10.1212\/WNL.0000000000005906","volume":"91","author":"AK Hedstr\u00f6m","year":"2018","unstructured":"Hedstr\u00f6m AK, H\u00f6ssjer O, Katsoulis M, Kockum I, Olsson T, Alfredsson L. Organic solvents and MS susceptibility. Neurology. 2018;91:e455\u201362. https:\/\/doi.org\/10.1212\/WNL.0000000000005906.","journal-title":"Neurology"},{"issue":"3","key":"1667_CR133","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3945\/an.116.014191","volume":"8","author":"M Jos\u00e9 Bagur","year":"2017","unstructured":"Bagur MJ, Murcia MA, Jim\u00e9nez-Monreal AM, Tur JA, Bibiloni MM, Alonso GL, et al. Influence of diet in multiple sclerosis: a systematic review. Adv Nutr An Int Rev J. 2017;8:463-47.","journal-title":"Advances in Nutrition: An International Review Journal"},{"key":"1667_CR134","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s12031-015-0660-0","volume":"58","author":"WW Wang","year":"2016","unstructured":"Wang WW, Lu L, Bao TH, Zhang HM, Yuan J, Miao W, et al. Scutellarin alleviates behavioral deficits in a mouse model of multiple sclerosis, possibly through protecting neural stem cells. J Mol Neurosci. 2016;58:210\u201320.","journal-title":"J Mol Neurosci"},{"key":"1667_CR135","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1084\/jem.20040819","volume":"200","author":"JJA Hendriks","year":"2004","unstructured":"Hendriks JJA, Alblas J, van der Pol SMA, van Tol EAF, Dijkstra CD, de Vries HE. Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis. J Exp Med. 2004;200:1667\u201372. https:\/\/doi.org\/10.1084\/jem.20040819.","journal-title":"J Exp Med"},{"key":"1667_CR136","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.jneuroim.2008.09.008","volume":"205","author":"Z Sternberg","year":"2008","unstructured":"Sternberg Z, Chadha K, Lieberman A, Hojnacki D, Drake A, Zamboni P, et al. Quercetin and interferon-\u03b2 modulate immune response(s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients. J Neuroimmunol. 2008;205:142\u20137. https:\/\/doi.org\/10.1016\/j.jneuroim.2008.09.008.","journal-title":"J Neuroimmunol"},{"issue":"8","key":"1667_CR137","doi-asserted-by":"publisher","first-page":"2329S","DOI":"10.1093\/jn\/132.8.2329S","volume":"132","author":"Sharon A. Ross","year":"2002","unstructured":"Ross SA, Poirier L. Proceedings of the Trans-HHS Workshop: diet, DNA methylation processes and health. J Nutr. 2002;132:2329S-2332S","journal-title":"The Journal of Nutrition"},{"key":"1667_CR138","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.bbrc.2013.09.010","volume":"439","author":"KM Dickson","year":"2013","unstructured":"Dickson KM, Gustafson CB, Young JI, Z\u00fcchner S, Wang G. Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate. Biochem Biophys Res Commun. 2013;439:522\u20137. https:\/\/doi.org\/10.1016\/j.bbrc.2013.09.010.","journal-title":"Biochem Biophys Res Commun"},{"key":"1667_CR139","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuint.2017.10.011","volume":"112","author":"NK Singhal","year":"2018","unstructured":"Singhal NK, Freeman E, Arning E, Wasek B, Clements R, Sheppard C, et al. Dysregulation of methionine metabolism in multiple sclerosis. Neurochem Int. 2018;112:1\u20134. https:\/\/doi.org\/10.1016\/j.neuint.2017.10.011.","journal-title":"Neurochem Int"},{"issue":"7","key":"1667_CR140","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1002\/art.37967","volume":"65","author":"Faith M. Strickland","year":"2013","unstructured":"Strickland FM, Hewagama A, Wu A, Sawalha AH, Delaney C, Hoeltzel MF, et al. Diet influences expression of autoimmune-associated genes and disease severity by epigenetic mechanisms in a transgenic mouse model of lupus. Arthritis Rheum. 2013;65:1872\u201381.","journal-title":"Arthritis & Rheumatism"},{"key":"1667_CR141","doi-asserted-by":"publisher","first-page":"15170","DOI":"10.1523\/JNEUROSCI.4349-14.2015","volume":"35","author":"NK Singhal","year":"2015","unstructured":"Singhal NK, Li S, Arning E, Alkhayer K, Clements R, Sarcyk Z, et al. Changes in methionine metabolism and histone H3 trimethylation are linked to mitochondrial defects in multiple sclerosis. J Neurosci. 2015;35:15170\u201386. https:\/\/doi.org\/10.1523\/JNEUROSCI.4349-14.2015.","journal-title":"J Neurosci"},{"key":"1667_CR142","doi-asserted-by":"crossref","unstructured":"Zhou X, Zhang L, Ji WJ, Yuan F, Guo ZZ, Pang B, et al. Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyteplatelet aggregates in humans: implications in end organ inflammation. PLoS One. 2013;8;e60332.","DOI":"10.1371\/journal.pone.0060332"},{"key":"1667_CR143","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1172\/JCI81151","volume":"125","author":"AL Hernandez","year":"2015","unstructured":"Hernandez AL, Kleinewietfeld M, David A, Hernandez AL, Kitz A, Wu C, et al. Sodium chloride inhibits the suppressive function of FOXP3 + regulatory T cells. J Clin Invest. 2015;125:4212\u201322.","journal-title":"J Clin Invest"},{"key":"1667_CR144","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jaut.2015.11.001","volume":"67","author":"S Hucke","year":"2016","unstructured":"Hucke S, Eschborn M, Liebmann M, Herold M, Freise N, Engbers A, et al. Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity. J Autoimmun. 2016;67:90\u2013101. https:\/\/doi.org\/10.1016\/j.jaut.2015.11.001.","journal-title":"J Autoimmun"},{"key":"1667_CR145","doi-asserted-by":"publisher","unstructured":"Zhang T, Fang S, Wan C, Kong Q, Wang G, Wang S, et al. Excess salt exacerbates blood-brain barrier disruption via a p38\/MAPK\/SGK1-dependent pathway in permanent cerebral ischemia. Sci Rep. 2015;5. https:\/\/doi.org\/10.1038\/srep16548.","DOI":"10.1038\/srep16548"},{"key":"1667_CR146","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1136\/jnnp-2014-307928","volume":"86","author":"MF Farez","year":"2015","unstructured":"Farez MF, Fiol MP, Gait\u00e1n MI, Quintana FJ, Correale J. Sodium intake is associated with increased disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2015;86:26\u201331.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1667_CR147","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-3-319-31248-4_3","volume":"902","author":"M Mischke","year":"2016","unstructured":"Mischke M, Pl\u00f6sch T. The gut microbiota and their metabolites: potential implications for the host epigenome. Adv Exp Med Biol. 2016;902:33\u201344.","journal-title":"Adv Exp Med Biol"},{"key":"1667_CR148","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature10554","volume":"479","author":"K Berer","year":"2011","unstructured":"Berer K, Mues M, Koutrolos M, AlRasbi Z, Boziki M, Johner C, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538\u201341. https:\/\/doi.org\/10.1038\/nature10554.","journal-title":"Nature"},{"issue":"Supplement_1","key":"1667_CR149","doi-asserted-by":"publisher","first-page":"4615","DOI":"10.1073\/pnas.1000082107","volume":"108","author":"YK Lee","year":"2011","unstructured":"Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci. 2011;108(Supplement_1):4615\u201322. https:\/\/doi.org\/10.1073\/pnas.1000082107.","journal-title":"Proc Natl Acad Sci"},{"key":"1667_CR150","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep28484","volume":"6","author":"J Chen","year":"2016","unstructured":"Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MMP, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep. 2016;6:1\u201310. https:\/\/doi.org\/10.1038\/srep28484.","journal-title":"Sci Rep"},{"key":"1667_CR151","doi-asserted-by":"publisher","first-page":"10719","DOI":"10.1073\/pnas.1711233114","volume":"114","author":"K Berer","year":"2017","unstructured":"Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, Xia Z, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci. 2017;114:10719\u201324.","journal-title":"Proc Natl Acad Sci"},{"issue":"7","key":"1667_CR152","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/ki.2011.445","volume":"81","author":"Chiao-Yin Sun","year":"2012","unstructured":"Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012;81:640\u201350.","journal-title":"Kidney International"},{"issue":"8","key":"1667_CR153","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/sj.ki.5002163","volume":"71","author":"P.-Ure\u00f1a Torres","year":"2007","unstructured":"Torres PU, Pri\u00e9 D, Molina-Bl\u00e9try V, Beck L, Silve C, Friedlander G. Klotho: An antiaging protein involved in mineral and vitamin D metabolism. Kidney Int. 2007;71:730\u20137.","journal-title":"Kidney International"},{"issue":"1","key":"1667_CR154","doi-asserted-by":"publisher","first-page":"52","DOI":"10.14336\/AD.2014.050052","volume":"5","author":"Igor Afanas\u2019ev","year":"2014","unstructured":"Afanas\u2019ev I. New nucleophilic mechanisms of Ros-dependent epigenetic modifications: comparison of aging and cancer. Aging Dis. 2014;5:52\u201362.","journal-title":"Aging and Disease"},{"issue":"8","key":"1667_CR155","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.jnutbio.2012.03.003","volume":"23","author":"Olivia S. Anderson","year":"2012","unstructured":"Anderson OS, Sant KE, Dolinoy DC. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem. 2012;23:853\u20139.","journal-title":"The Journal of Nutritional Biochemistry"},{"key":"1667_CR156","doi-asserted-by":"crossref","unstructured":"Kalhan SC. One-carbon metabolism, fetal growth and long-term consequences. In: Nestle Nutrition Institute Workshop Series; 2013.","DOI":"10.1159\/000348459"},{"issue":"3","key":"1667_CR157","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1158\/0008-5472.CAN-10-2379","volume":"71","author":"A. Ly","year":"2010","unstructured":"Ly A, Lee H, Chen J, Sie KKY, Renlund R, Medline A, et al. Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring. Cancer Res. 2011;71:988\u201397.","journal-title":"Cancer Research"},{"issue":"33","key":"1667_CR158","doi-asserted-by":"publisher","first-page":"12511","DOI":"10.1073\/pnas.0601056103","volume":"103","author":"M.-E. Dumas","year":"2006","unstructured":"Dumas M-E, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci. 2006;103:12511\u20136.","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"9","key":"1667_CR159","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1093\/hmg\/ddr044","volume":"20","author":"Tiffany D. Schaible","year":"2011","unstructured":"Schaible TD, Harris RA, Dowd SE, Smith CW, Kellermayer R. Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes. Hum Mol Genet. 2011;20:1687\u201396.","journal-title":"Human Molecular Genetics"},{"key":"1667_CR160","unstructured":"Canani RB, Costanzo MD, Leone L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics. 2012;4:1\u20137."},{"issue":"12","key":"1667_CR161","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1093\/carcin\/bgm206","volume":"28","author":"Y. Kanai","year":"2007","unstructured":"Kanai Y, Hirohashi S. Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis. 2007;28:2434\u201342.","journal-title":"Carcinogenesis"},{"issue":"2","key":"1667_CR162","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s10620-010-1312-4","volume":"56","author":"Daniel L. Worthley","year":"2010","unstructured":"Worthley DL, Whitehall VLJ, Le Leu RK, Irahara N, Buttenshaw RL, Mallitt KA, et al. DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids. Dig Dis Sci. 2011;56:387\u201396.","journal-title":"Digestive Diseases and Sciences"},{"issue":"6","key":"1667_CR163","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.sbi.2010.09.006","volume":"20","author":"Haifeng Hou","year":"2010","unstructured":"Hou H, Yu H. Structural insights into histone lysine demethylation. Curr Opin Struct Biol. 2010;20:739-48.","journal-title":"Current Opinion in Structural Biology"},{"key":"1667_CR164","doi-asserted-by":"crossref","unstructured":"Wang L, Chang J, Varghese D, Dellinger M, Kumar S, Best AM, et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035.","DOI":"10.1038\/ncomms3035"},{"issue":"19","key":"1667_CR165","doi-asserted-by":"publisher","first-page":"13669","DOI":"10.1074\/jbc.C113.464800","volume":"288","author":"Emily A. Minor","year":"2013","unstructured":"Minor EA, Court BL, Young JI, Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem. 2013;288:13669\u201374.","journal-title":"Journal of Biological Chemistry"},{"key":"1667_CR166","doi-asserted-by":"crossref","unstructured":"Kumar H, Lund R, Laiho A, Lundelin K, Ley RE, Isolauri E, et al. Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis. MBio. 2014;5:e02113\u201314.","DOI":"10.1128\/mBio.02113-14"},{"key":"1667_CR167","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1152\/japplphysiol.00878.2014","volume":"118","author":"J Denham","year":"2015","unstructured":"Denham J, O\u2019Brien BJ, Marques FZ, Charchar FJ. Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise. J Appl Physiol. 2015;118:475\u201388. https:\/\/doi.org\/10.1152\/japplphysiol.00878.2014.","journal-title":"J Appl Physiol"},{"key":"1667_CR168","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1752-8062.2011.00384.x","volume":"5","author":"S Radom-Aizik","year":"2012","unstructured":"Radom-Aizik S, Zaldivar F, Leu SY, Adams GR, Oliver S, Cooper DM. Effects of exercise on microRNA expression in young males peripheral blood mononuclear cells. Clin Transl Sci. 2012;5:32\u20138.","journal-title":"Clin Transl Sci"},{"key":"1667_CR169","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/j.1460-9568.2010.07508.x","volume":"33","author":"F Gomez-Pinilla","year":"2011","unstructured":"Gomez-Pinilla F, Zhuang Y, Feng J, Ying Z, Fan G. Exercise impacts brain-derived neurotrophic factor plasticity by engaging mechanisms of epigenetic regulation. Eur J Neurosci. 2011;33:383\u201390.","journal-title":"Eur J Neurosci"},{"key":"1667_CR170","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jneuroim.2016.08.007","volume":"299","author":"S Briken","year":"2016","unstructured":"Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, et al. Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol. 2016;299:53\u20138. https:\/\/doi.org\/10.1016\/j.jneuroim.2016.08.007.","journal-title":"J Neuroimmunol"},{"issue":"1","key":"1667_CR171","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1146\/annurev.ne.19.030196.001445","volume":"19","author":"Gary R. Lewin","year":"1996","unstructured":"Lewin GR. Physiology of the Neurotrophins. Annu Rev Neurosci. 1996;19:289\u2013317.","journal-title":"Annual Review of Neuroscience"},{"key":"1667_CR172","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/brain\/awf015","volume":"125","author":"C Stadelmann","year":"2002","unstructured":"Stadelmann C, Kerschensteiner M, Misgeld T, Br\u00fcck W, Hohlfeld R, Lassmann H. BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain. 2002;125:75\u201385.","journal-title":"Brain"},{"issue":"5","key":"1667_CR173","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1084\/jem.189.5.865","volume":"189","author":"Martin Kerschensteiner","year":"1999","unstructured":"Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, et al. Activated human T cells, B cells, and monocytes produce brainderived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med. 1999;189:865\u201370.","journal-title":"The Journal of Experimental Medicine"},{"key":"1667_CR174","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1111\/j.1460-9568.2004.03720.x","volume":"20","author":"S Vaynman","year":"2004","unstructured":"Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004;20:2580\u201390.","journal-title":"Eur J Neurosci"},{"issue":"3","key":"1667_CR175","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1159\/000323170","volume":"18","author":"Junhua Xiao","year":"2010","unstructured":"Xiao J, Wong AW, Willingham MM, Van Den Buuse M, Kilpatrick TJ, Murray SS. Brain-derived neurotrophic factor promotes central nervous system myelination via a direct effect upon oligodendrocytes. NeuroSignals. 2011;18:186\u2013202.","journal-title":"Neurosignals"},{"issue":"1","key":"1667_CR176","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s12035-016-0344-y","volume":"55","author":"Christina A. E. S\u00f8lvsten","year":"2016","unstructured":"S\u00f8lvsten CAE, De Paoli F, Christensen JH, Nielsen AL. Voluntary physical exercise induces expression and epigenetic remodeling of VegfA in the rat hippocampus. Mol Neurobiol. 2016;55:567\u201382.","journal-title":"Molecular Neurobiology"},{"issue":"1","key":"1667_CR177","doi-asserted-by":"publisher","first-page":"70","DOI":"10.4103\/1673-5374.198982","volume":"12","author":"Wensheng Lin","year":"2017","unstructured":"Lin W. Neuroprotective effects of vascular endothelial growth factor A in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Neural Regen Res. 2017;12:70\u20131.","journal-title":"Neural Regeneration Research"},{"key":"1667_CR178","doi-asserted-by":"crossref","unstructured":"Keane RW, Dietrich WD, de Rivero Vaccari JP. Inflammasome proteins as biomarkers of multiple sclerosis. Front Neurol. 2018;9:135.","DOI":"10.3389\/fneur.2018.00135"},{"issue":"09","key":"1667_CR179","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1055\/s-0029-1246140","volume":"31","author":"K. Nakajima","year":"2010","unstructured":"Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, et al. Exercise effects on methylation of ASC gene. Int J Sports Med. 2010;31:671\u20135.","journal-title":"International Journal of Sports Medicine"},{"issue":"3","key":"1667_CR180","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/ijc.22342","volume":"120","author":"Martha L. Slattery","year":"2006","unstructured":"Slattery ML, Curtin K, Sweeney C, Levin TR, Potter J, Wolff RK, et al. Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer. Int J Cancer. 2006;120:656\u201363.","journal-title":"International Journal of Cancer"},{"issue":"3","key":"1667_CR181","doi-asserted-by":"publisher","first-page":"293","DOI":"10.4161\/epi.6.3.14378","volume":"6","author":"Fang Fang Zhang","year":"2011","unstructured":"Zhang FF, Cardarelli R, Carroll J, Zhang S, Fulda KG, Gonzalez K, et al. Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics. 2011;6:293\u20139.","journal-title":"Epigenetics"},{"issue":"9","key":"1667_CR182","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1016\/j.ejca.2013.02.013","volume":"49","author":"Alexandra J. White","year":"2013","unstructured":"White AJ, Sandler DP, Bolick SCE, Xu Z, Taylor JA, Deroo LA. Recreational and household physical activity at different time points and DNA global methylation. Eur J Cancer. 2013;49:2199\u2013206. http:\/\/sci-hub.tw\/10.1016\/j.ejca.2013.02.013.","journal-title":"European Journal of Cancer"},{"issue":"7442","key":"1667_CR183","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1136\/bmj.38041.724421.55","volume":"328","author":"David C Mohr","year":"2004","unstructured":"Mohr DC. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ. 2004;328:731. http:\/\/scihub.tw\/10.1136\/bmj.38041.724421.55.","journal-title":"BMJ"},{"issue":"3","key":"1667_CR184","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1159\/000226428","volume":"62","author":"X.J. Liu","year":"2009","unstructured":"Liu XJ, Ye HX, Li WP, Dai R, Chen D, Jin M. Relationship between psychosocial factors and onset of multiple sclerosis. Eur Neurol. 2009;62:130\u20136.","journal-title":"European Neurology"},{"key":"1667_CR185","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neubiorev.2014.11.013","volume":"48","author":"Olena Babenko","year":"2015","unstructured":"Babenko O, Kovalchuk I, Metz GAS. Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neurosci Biobehav Rev. 2015;48:70\u201391. http:\/\/sci-hub.tw\/10.1016\/j.neubiorev.2014.11.013.","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"1667_CR186","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.12688\/f1000research.11375.1","volume":"6","author":"Michael J. Garabedian","year":"2017","unstructured":"Garabedian MJ, Harris CA, Jeanneteau F. Glucocorticoid receptor action in metabolic and neuronal function. F1000Res. 2017;6:1208. http:\/\/scihub.tw\/10.12688\/f1000research.11375.1.","journal-title":"F1000Research"},{"issue":"7","key":"1667_CR187","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1177\/1352458508090666","volume":"14","author":"M Matysiak","year":"2008","unstructured":"Matysiak M, Makosa B, Walczak A, Selmaj K. Patients with multiple sclerosis resisted to glucocorticoid therapy: abnormal expression of heat-shock protein 90 in glucocorticoid receptor complex. Mult Scler. 2008;14:919\u201326.","journal-title":"Multiple Sclerosis Journal"},{"issue":"4","key":"1667_CR188","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","volume":"164","author":"Cris S Constantinescu","year":"2011","unstructured":"Constantinescu CS, Farooqi N, O\u2019Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164:1079\u2013106.","journal-title":"British Journal of Pharmacology"},{"key":"1667_CR189","doi-asserted-by":"crossref","unstructured":"Barthelmes J, Tafferner N, Kurz J, de Bruin N, Parnham MJ, Geisslinger G, et al. Induction of experimental autoimmune encephalomyelitis in mice and evaluation of the disease-dependent distribution of immune cells in various tissues. J Vis Exp. 2016:1\u201310. http:\/\/dx.doi.org\/10.3791\/53933.","DOI":"10.3791\/53933"},{"issue":"11","key":"1667_CR190","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.15252\/emmm.201404168","volume":"6","author":"Katja Schmitz","year":"2014","unstructured":"Schmitz K, de Bruin N, Bishay P, Mannich J, Haussler A, Altmann C, et al. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice. EMBO Mol Med. 2014;6:1398\u2013422. http:\/\/dx.doi.org\/10.15252\/emmm.201404168.","journal-title":"EMBO Molecular Medicine"},{"key":"1667_CR191","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.jneuroim.2016.03.009","volume":"294","author":"G. Catanzaro","year":"2016","unstructured":"Catanzaro G, Pucci M, Viscomi MT, Lanuti M, Feole M, Angeletti S, et al. Epigenetic modifications of Dexras 1 along the nNOS pathway in an animal model of multiple sclerosis. J Neuroimmunol. 2016;294:32\u201340. http:\/\/dx.doi.org\/10.1016\/j.jneuroim.2016.03.009.","journal-title":"Journal of Neuroimmunology"},{"key":"1667_CR192","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jns.2017.01.060","volume":"375","author":"Ali Noori-Zadeh","year":"2017","unstructured":"Noori-Zadeh A, Mesbah-Namin SA, Saboor-Yaraghi AA. Epigenetic and gene expression alterations of FOXP3 in the T cells of EAE mouse model of multiple sclerosis. J Neurol Sci. 2017;375:203\u20138.","journal-title":"Journal of the Neurological Sciences"},{"key":"1667_CR193","unstructured":"Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. J Immunol. 2017;198:986\u201392."},{"key":"1667_CR194","unstructured":"Blakemore WF, Franklin RJM. Remyelination in experimental models of toxin-induced demyelination. Curr Top Microbiol Immunol. 2008;318:193\u2013212."},{"issue":"1","key":"1667_CR195","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1750-3639.2001.tb00385.x","volume":"11","author":"Glenn K. Matsushima","year":"2006","unstructured":"Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 2001;11:107\u201316.","journal-title":"Brain Pathology"},{"issue":"2","key":"1667_CR196","doi-asserted-by":"publisher","first-page":"ENEURO.0336-16.","DOI":"10.1523\/ENEURO.0336-16.2017","volume":"4","author":"Sarah Moyon","year":"2017","unstructured":"Moyon S, Ma D, Huynh JL, Coutts DJC, Zhao C, Casaccia P, et al. Efficient remyelination requires DNA methylation. eneuro. 2017;4:ENEURO.0336\u201316.2017.","journal-title":"eneuro"},{"key":"1667_CR197","doi-asserted-by":"publisher","first-page":"13669","DOI":"10.1074\/jbc.C113.464800","volume":"288","author":"EA Minor","year":"2013","unstructured":"Minor EA, Court BL, Young JI, Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J Biol Chem. 2013;288:13669\u201374.","journal-title":"J Biol Chem"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1667-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-019-1667-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1667-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T23:20:41Z","timestamp":1722295241000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-019-1667-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,14]]},"references-count":197,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1667"],"URL":"https:\/\/doi.org\/10.1186\/s12974-019-1667-1","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,14]]},"assertion":[{"value":"3 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors read and approved the final manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}