{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:16:05Z","timestamp":1785330965604,"version":"3.55.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Science and Technology Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010828","name":"Department of Education of Guizhou Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Science and Technology Department","doi-asserted-by":"publisher","award":["QKH-PTRC-2017-5733-003"],"award-info":[{"award-number":["QKH-PTRC-2017-5733-003"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Beh\u00e7et\u2019s disease (BD) is a chronic refractory multisystem autoinflammatory disease, characterized by typical clinical features of non-specific vasculitis, oral and genital ulcers, uveitis, as well as skin lesions. The exact etiopathogenesis of BD remains unknown, existing studies have indicated that genetics and environmental factors contribute to the increased development of BD. Recently, several studies have shown that external environmental factors can affect the process of epigenetic modification, and abnormalities of epigenetic factors have been confirmed to be involved in the occurrence of BD. At the same time, abnormalities of gut microbiota (GM) in the body, have also been confirmed to participate in the pathogenesis of BD by regulating the balance of Th17\/Tregs. This article reviews the pathogenesis of BD and summarizes numerous clinical studies, focusing on the mechanism of GM and epigenetic factors impacting on BD, and providing new ideas for further elucidating the pathogenesis of BD.<\/jats:p>","DOI":"10.3389\/fcell.2021.719235","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T14:02:06Z","timestamp":1633442526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Critical Role of Gut Microbiota and Epigenetic Factors in the Pathogenesis of Beh\u00e7et\u2019s Disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Xiaomin","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangbing","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.imlet.2018.07.001","article-title":"Evaluation of SOCS1 methylation in patients with Beh\u00e7et\u2019s disease.","volume":"203","author":"Abdi","year":"2018","journal-title":"Immunol. Lett."},{"key":"B2","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/ni1496","article-title":"Interleukins 1\u03b2 and 6 but not transforming growth factor-\u03b2 are essential for the differentiation of interleukin 17\u2013producing human T helper cells.","volume":"8","author":"Acosta-Rodriguez","year":"2007","journal-title":"Nat. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3985","DOI":"10.1002\/jcp.27207","article-title":"Disturbed Th17\/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Beh\u00e7et\u2019s disease.","volume":"234","author":"Ahmadi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-020-00912-9","article-title":"Epigenetics for Clinicians from the Perspective of Pediatric Rheumatic Diseases.","volume":"22","author":"Akbaba","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6614","DOI":"10.1002\/jcb.26809","article-title":"Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Beh\u00e7et\u2019s disease.","volume":"119","author":"Alipour","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"B6","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.biopha.2017.04.106","article-title":"Epigenetic alterations in chronic disease focusing on Beh\u00e7et\u2019s disease: review.","volume":"91","author":"Alipour","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.reuma.2018.06.006","article-title":"Methylation Status of Interleukin-6 Gene Promoter in Patients with Beh\u00e7et\u2019s Disease.","volume":"16","author":"Alipour","year":"2020","journal-title":"Reumatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrg.2016.59","article-title":"The molecular hallmarks of epigenetic control.","volume":"17","author":"Allis","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1042\/EBC20190030","article-title":"Enhancer DNA methylation: implications for gene regulation.","volume":"63","author":"Angeloni","year":"2019","journal-title":"Essays Biochem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/iji.12473","article-title":"Promoter methylation of Bax and Bcl2 genes and their expression in patients with Beh\u00e7et\u2019s disease.","volume":"47","author":"Asadi","year":"2020","journal-title":"Int. J. Immunogenet."},{"key":"B12","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1080\/1354750X.2020.1754912","article-title":"The methylation status of TNF-\u03b1 and SOCS3 promoters and the regulation of these gene expressions in patients with Beh\u00e7et\u2019s disease.","volume":"25","author":"Aziz","year":"2020","journal-title":"Biomarkers"},{"key":"B13","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications.","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell. Res."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/2516865720947014","article-title":"An Understudied Dimension:Why Age Needs to Be Considered When Studying Epigenetic-Environment Interactions.","volume":"13","author":"Barrere-Cain","year":"2020","journal-title":"Epigenet. Insights"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1624-x","article-title":"Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study.","volume":"20","author":"Bartlett","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1128\/MCB.01206-10","article-title":"Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs allograft survival.","volume":"31","author":"Beier","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"B17","first-page":"S43","article-title":"Toll-like receptor 4 (TLR4) gene polymorphisms in Italian patients with Beh\u00e7et\u2019s disease.","volume":"27","author":"Boiardi","year":"2009","journal-title":"Clin. Exp. Rheumatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1002\/eji.202048876","article-title":"Crossing the barriers: revisiting the gut feeling in rheumatoid arthritis.","volume":"51","author":"Brandl","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"B19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/JLB.2RU1118-422R","article-title":"). Sirtuin\u22121 in immunotherapy: a Janus\u2212headed target.","volume":"106","author":"Chadha","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"40364","DOI":"10.1074\/jbc.M509329200","article-title":"SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling.","volume":"280","author":"Chen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1080\/09273948.2016.1189577","article-title":"Patterns and Etiologies of Uveitis at a Tertiary Referral Center in Taiwan.","volume":"25","author":"Chen","year":"2017","journal-title":"Ocul. Immunol. Inflamm."},{"key":"B22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3349\/ymj.2012.53.1.35","article-title":"New insights in the clinical understanding of Beh\u00e7et\u2019s disease.","volume":"53","author":"Cho","year":"2012","journal-title":"Yonsei Med. J."},{"key":"B23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/BOR.0000000000000451","article-title":"An update on the role of epigenetics in systemic vasculitis.","volume":"30","author":"Coit","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.autrev.2014.11.009","article-title":"Beh\u00e7et\u2019s syndrome patients exhibit specific microbiome signature.","volume":"14","author":"Consolandi","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"B25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jneuroim.2010.06.009","article-title":"Altered miRNA expression in T regulatory cells in course of multiple sclerosis.","volume":"226","author":"De Santis","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/sji.12261","article-title":"The Role of MicroRNAs in Autoimmune Diseases with Skin Involvement.","volume":"81","author":"Deng","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1093\/nar\/10.8.2709","article-title":"Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells.","volume":"10","author":"Ehrlich","year":"1982","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jaut.2013.01.011","article-title":"SIRT1 activation protects against autoimmune T cell-driven retinal disease in mice via inhibition of IL-2\/Stat5 signaling.","volume":"42","author":"Gardner","year":"2013","journal-title":"J. Autoimmun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/s0181-5512(06)73762-7","article-title":"Production des cytokines Th1\/Th2 et du monoxyde d\u2019azote au cours de l\u2019uv\u00e9ite \"Beh\u00e7et\" et de l\u2019uv\u00e9ite \"idiopathique\" [Production of Th1\/Th2 cytokines and nitric oxide in Beh\u00e7et\u2019s uveitis and idiopathic uveitis].","volume":"29","author":"Guenane","year":"2006","journal-title":"J. Fr. Ophtalmol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"CR227","DOI":"10.12659\/msm.881720","article-title":"Expression of Th-17 and ROR\u03b3t mRNA in Beh\u00e7et\u2019s Disease.","volume":"17","author":"Hamzaoui","year":"2011","journal-title":"Med. Sci. Monit."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1080\/13880209.2021.1954667","article-title":"Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db\/db mice.","volume":"59","author":"Han","year":"2021","journal-title":"Pharm. Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.1742-7843.2007.00186.x","article-title":"Developmental origins of health and disease: new insights.","volume":"102","author":"Hanson","year":"2008","journal-title":"Basic. Clin. Pharmacol. Toxicol."},{"key":"B33","first-page":"3","article-title":"One year in review 2019: beh\u00e7et\u2019s syndrome.","volume":"37","author":"Hatemi","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01703","article-title":"Microbiome and Metabolome Analyses Reveal the Disruption of Lipid Metabolism in Systemic Lupus Erythematosus.","volume":"11","author":"He","year":"2020","journal-title":"Front. Immunol."},{"key":"B35","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1093\/rheumatology\/kep077","article-title":"Association of TLR4 polymorphisms with Behcet\u2019s disease in a Korean population.","volume":"48","author":"Horie","year":"2009","journal-title":"Rheumatology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107853","article-title":"Uveitis genetics.","volume":"190","author":"Hou","year":"2020","journal-title":"Exp. Eye Res."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/ar3789","article-title":"Replication study confirms the association between UBAC2 and Beh\u00e7et\u2019s disease in two independent Chinese sets of patients and controls.","volume":"14","author":"Hou","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.clim.2008.06.006","article-title":"SUMO4 gene polymorphisms in Chinese Han patients with Beh\u00e7et\u2019s disease.","volume":"129","author":"Hou","year":"2008","journal-title":"Clin. Immunol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24408","article-title":"Significant Decline in the Incidence of Behcet\u2019s Disease in South Korea: a Nationwide Population-Based Study (2004-2017).","author":"Jun","year":"2020","journal-title":"Arthritis Care Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.imlet.2017.08.008","article-title":"Interleukin-26 is overexpressed in Beh\u00e7et\u2019s disease and enhances Th17 related -cytokines.","volume":"190","author":"Kaabachi","year":"2017","journal-title":"Immunol. Lett"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.imlet.2019.05.004","article-title":"Th 9 cells in Beh\u00e7et disease: possible involvement of IL-9 in pulmonary manifestations.","volume":"211","author":"Kaabachi","year":"2019","journal-title":"Immunol. Lett"},{"key":"B42","first-page":"S45","article-title":"Association of small ubiquitin-like modifier 4 (SUMO4) polymorphisms in a Tunisian population with Beh\u00e7et\u2019s disease.","volume":"28","author":"Kamoun","year":"2010","journal-title":"Clin. Exp. Rheumatol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1002\/art.21060","article-title":"Whole-genome screening for susceptibility genes in multicase families with Beh\u00e7et\u2019s disease.","volume":"52","author":"Karasneh","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3234","article-title":"Evaluation of DNA methylation status of toll\u2212like receptors 2 and 4 promoters in Behcet\u2019s disease.","volume":"22","author":"Kolahi","year":"2020","journal-title":"J. Gene Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.1167\/iovs.08-2666","article-title":"Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage andnuclear factor-kappaB activation.","volume":"50","author":"Kubota","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01067","article-title":"Beh\u00e7et\u2019s Disease: an Overview of Etiopathogenesis.","volume":"10","author":"Leccese","year":"2019","journal-title":"Front. Immunol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02517-8","article-title":"Decreased microRNA-155 in Behcet\u2019s disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production.","volume":"23","author":"Liang","year":"2021","journal-title":"Arthritis Res. Ther"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00200","article-title":"Cytokine Signatures in Mucocutaneous and Ocular Beh\u00e7et\u2019s Disease.","volume":"8","author":"Lopalco","year":"2017","journal-title":"Front. Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1080\/16078454.2020.1757332","article-title":"Identification of potential miRNA-mRNA interaction network in bone marrow T cells of acquired aplastic anemia.","volume":"25","author":"Lu","year":"2020","journal-title":"Hematology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/rheumatology\/kew486","article-title":"Exploring the variability in Beh\u00e7et\u2019s disease prevalence: a meta-analytical approach.","volume":"57","author":"Maldini","year":"2018","journal-title":"Rheumatology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1136\/ard.2007.079871","article-title":"Association of the toll-like receptor 4 gene polymorphisms with Behcet\u2019s disease.","volume":"67","author":"Meguro","year":"2008","journal-title":"Ann. Rheum. Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/BOR.0000000000000234","article-title":"Genetics of Beh\u00e7et\u2019s disease.","volume":"28","author":"Morton","year":"2016","journal-title":"Curr. Opin. Rheumatol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2174\/1573397114666180521090335","article-title":"Genetics and Epigenetics Mechanism in the Pathogenesis of Beh\u00e7et\u2019s Disease.","volume":"15","author":"Muhammad","year":"2019","journal-title":"Curr. Rheumatol. Rev."},{"key":"B54","first-page":"S56","article-title":"MicroRNA-155 regulates the Th17 immune response by targeting Ets-1 in Beh\u00e7et\u2019s disease.","volume":"34","author":"Na","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40824-y","article-title":"The association analysis between HLA-A*26 and Beh\u00e7et\u2019s disease.","volume":"9","author":"Nakamura","year":"2019","journal-title":"Sci. Rep."},{"key":"B56","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1007\/s10165-008-0064-x","article-title":"Decreased percentages of regulatory T cells in peripheral blood of patients with Beh\u00e7et\u2019s disease before ocular attack: a possible predictive marker of ocular attack.","volume":"18","author":"Nanke","year":"2008","journal-title":"Mod. Rheumatol."},{"key":"B57","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-2249.2008.03626.x","article-title":"Involvement of innate immunity in the pathogenesis of intestinal Beh\u00e7et\u2019s disease.","volume":"152","author":"Nara","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"B58","first-page":"58","article-title":"Microbiota stratification identifies disease-specific alterations in neuro-Beh\u00e7et\u2019s disease and multiple sclerosis.","volume":"37","author":"Oezguen","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.625710","article-title":"Genetics of Beh\u00e7et\u2019s Disease: functional Genetic Analysis and Estimating Disease Heritability.","volume":"8","author":"Ortiz-Fern\u00e1ndez","year":"2021","journal-title":"Front. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nature13823","article-title":"Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.","volume":"514","author":"Pickard","year":"2014","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2405150","article-title":"MicroRNA Expression Profiling in Beh\u00e7et\u2019s Disease.","volume":"2018","author":"Puccetti","year":"2018","journal-title":"J. Immunol. Res."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1007\/s00439-013-1346-8","article-title":"A functional variant of pre-miRNA-196a2 confers risk for Behcet\u2019s disease but not for Vogt-Koyanagi-Harada syndrome or AAU in ankylosing spondylitis.","volume":"132","author":"Qi","year":"2013","journal-title":"Hum. Genet."},{"key":"B63","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1093\/rheumatology\/ket438","article-title":"Increased Notch pathway activation in Beh\u00e7et\u2019s disease.","volume":"53","author":"Qi","year":"2014","journal-title":"Rheumatology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s12016-015-8495-6","article-title":"Epigenetics and Vasculitis: a Comprehensive Review.","volume":"50","author":"Renauer","year":"2016","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nri2515","article-title":"The gut microbiota shapes intestinal immune responses during health and disease.","volume":"9","author":"Round","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153746","article-title":"Bifidobacteria Abundance-Featured Gut Microbiota Compositional Change in Patients with Beh\u00e7et\u2019s disease.","volume":"11","author":"Shimizu","year":"2016","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s10067-018-04419-8","article-title":"Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Beh\u00e7et\u2019s disease (210 characters).","volume":"38","author":"Shimizu","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113783","article-title":"Genome-Wide Identification of Epigenetic Regulators in Quercus suber L.","volume":"21","author":"Silva","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"5216","DOI":"10.1093\/emboj\/cdf516","article-title":"Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene.","volume":"21","author":"Sun","year":"2002","journal-title":"EMBO J"},{"key":"B70","doi-asserted-by":"publisher","first-page":"12481","DOI":"10.1073\/pnas.0605298103","article-title":"NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses.","volume":"103","author":"Taganov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B71","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/ng.3786","article-title":"Dense genotyping of immune-related loci implicates host responses to microbial exposure in Beh\u00e7et\u2019s disease susceptibility.","volume":"49","author":"Takeuchi","year":"2017","journal-title":"Nat. Genet."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0241691","article-title":"Succinivibrionaceae is dominant family in fecal microbiota of Beh\u00e7et\u2019s Syndrome patients with uveitis.","volume":"15","author":"Tecer","year":"2020","journal-title":"PLoS One"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1002\/art.21145","article-title":"NF-\u03baB protects Beh\u00e7et\u2019s disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins.","volume":"52","author":"Todaro","year":"2005","journal-title":"Arthritis Rheum."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01192","article-title":"Beh\u00e7et\u2019s Disease Under Microbiotic Surveillance? A Combined Analysis of Two Cohorts of Beh\u00e7et\u2019s Disease Patients.","volume":"11","author":"van der Houwen","year":"2020","journal-title":"Front. Immunol."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.20643","article-title":"Lesional activation of Tc 17 cells in Beh\u00e7et\u2019s disease and psoriasis supports HLA-class I-mediated autoimmune responses.","author":"Vural","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/ni1497","article-title":"Development, cytokine profile and function of human interleukin 17\u2013producing helper T cells.","volume":"8","author":"Wilson","year":"2007","journal-title":"Nat. Immunol."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-016-0130-7","article-title":"MicroRNAs differentially expressed in Beh\u00e7et disease are involved in interleukin-6 production.","volume":"13","author":"Woo","year":"2016","journal-title":"J. Inflamm."},{"key":"B78","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1136\/annrheumdis-2013-204475","article-title":"FUT2: filling the gap between genes and environment in Beh\u00e7et\u2019s disease?","volume":"74","author":"Xavier","year":"2015","journal-title":"Ann. Rheum. Dis"},{"key":"B79","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-00877-3","article-title":"Comprehensive analysis of the association between UBAC2 polymorphisms and Beh\u00e7et\u2019s disease in a Japanese population.","volume":"7","author":"Yamazoe","year":"2017","journal-title":"Sci. Rep."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8813558","article-title":"The Function and Role of the Th17\/Treg Cell Balance in Inflammatory Bowel Disease.","volume":"2020","author":"Yan","year":"2020","journal-title":"J. Immunol. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1136\/bjophthalmol-2020-315960","article-title":"Prevalence and clinical features of systemic diseases in Chinese patients with uveitis.","volume":"105","author":"Yang","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbpa.2019.01.024","article-title":"The roles of microRNAs in epigenetic regulation.","volume":"51","author":"Yao","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0520-6","article-title":"A metagenomic study of the gut microbiome in Beh\u00e7et\u2019s disease.","volume":"6","author":"Ye","year":"2018","journal-title":"Microbiome"},{"key":"B84","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1038\/sj.emboj.7600244","article-title":"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase.","volume":"23","author":"Yeung","year":"2004","journal-title":"EMBO J."},{"key":"B85","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/j.1348-0421.1992.tb02083.x","article-title":"Antibody response to oral streptococci in Beh\u00e7et\u2019s disease.","volume":"36","author":"Yokota","year":"1992","journal-title":"Microbiol. Immunol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1093\/rheumatology\/kez043","article-title":"Epigenome-wide association study identifies Beh\u00e7et\u2019s disease-associated methylation loci in Han Chinese.","volume":"58","author":"Yu","year":"2019","journal-title":"Rheumatology"},{"key":"B87","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1007\/s00109-014-1159-9","article-title":"Predisposition to Beh\u00e7et\u2019s disease and VKH syndrome by genetic variants of miR-182.","volume":"92","author":"Yu","year":"2014","journal-title":"J. Mol. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1167\/iovs.17-23247","article-title":"Association of Long Noncoding RNAs Polymorphisms With Ankylosing Spondylitis, Vogt-Koyanagi-Harada Disease, and Beh\u00e7et\u2019s disease.","volume":"59","author":"Yue","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02125-1","article-title":"Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients.","volume":"21","author":"Zhang","year":"2021","journal-title":"BMC Microbiol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"5665","DOI":"10.1167\/iovs.12-9832","article-title":"Decreased microRNA-155 expression in ocular Beh\u00e7et\u2019s disease but not in Vogt Koyanagi Harada syndrome.","volume":"53","author":"Zhou","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"64263","DOI":"10.18632\/oncotarget.19500","article-title":"Aberrant DNA methylation of GATA binding protein 3 (GATA3), interleukin-4 (IL-4), and transforming growth factor-\u03b2 (TGF-\u03b2) promoters in Beh\u00e7et\u2019s disease.","volume":"8","author":"Zhu","year":"2017","journal-title":"Oncotarget"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.719235\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T14:02:37Z","timestamp":1633442557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.719235\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":91,"alternative-id":["10.3389\/fcell.2021.719235"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.719235","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,5]]},"article-number":"719235"}}