{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:25:17Z","timestamp":1789953917311,"version":"4.0.1"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TNF-\u03b1 antagonists provide benefit to patients with inflammatory autoimmune disorders such as Crohn\u2019s disease, rheumatoid arthritis, and ankylosing spondylitis. However, TNF antagonism unexplainably exacerbates CNS autoimmunity, including multiple sclerosis and neuromyelitis optica. The underlying mechanisms remain enigmatic. We demonstrate that TNFR2 deficiency results in female-biased spontaneous autoimmune CNS demyelination in myelin oligodendrocyte glycoprotein\u2013specific 2D2 TCR transgenic mice. Disease in TNFR2\u2212\/\u2212 2D2 mice was associated with CNS infiltration of T and B cells as well as increased production of myelin oligodendrocyte glycoprotein\u2013specific IL-17, IFN-\u03b3, and IgG2b. Attenuated disease in TNF\u2212\/\u2212 2D2 mice relative to TNFR2\u2212\/\u2212 2D2 mice identified distinctive roles for TNFR1 and TNFR2. Oral antibiotic treatment eliminated spontaneous autoimmunity in TNFR2\u2212\/\u2212 2D2 mice to suggest role for gut microbiota. Illumina sequencing of fecal 16S rRNA identified a distinct microbiota profile in male TNFR2\u2212\/\u2212 2D2 that was associated with disease protection. Akkermansia muciniphila, Sutterella sp., Oscillospira sp., Bacteroides acidifaciens, and Anaeroplasma sp. were selectively more abundant in male TNFR2\u2212\/\u2212 2D2 mice. In contrast, Bacteroides sp., Bacteroides uniformis, and Parabacteroides sp. were more abundant in affected female TNFR2\u2212\/\u2212 2D2 mice, suggesting a role in disease causation. Overall, TNFR2 blockade appears to disrupt commensal bacteria\u2013host immune symbiosis to reveal autoimmune demyelination in genetically susceptible mice. Under this paradigm, microbes likely contribute to an individual\u2019s response to anti-TNF therapy. This model provides a foundation for host immune\u2013microbiota-directed measures for the prevention and treatment of CNS-demyelinating autoimmune disorders.<\/jats:p>","DOI":"10.4049\/jimmunol.1501664","type":"journal-article","created":{"date-parts":[[2015,10,17]],"date-time":"2015-10-17T00:52:32Z","timestamp":1445043152000},"page":"4668-4684","source":"Crossref","is-referenced-by-count":60,"title":["TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease"],"prefix":"10.1093","volume":"195","author":[{"given":"Patrick G","family":"Miller","sequence":"first","affiliation":[{"name":"Laboratory of TGF-\u03b2 Biology, Epigenetics, and Cytokine Regulation, Center for Cellular and Molecular Immunology, Department of Surgery, University of Missouri School of Medicine , Columbia, MO 65212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B","family":"Bonn","sequence":"additional","affiliation":[{"name":"Laboratory of TGF-\u03b2 Biology, Epigenetics, and Cytokine Regulation, Center for Cellular and Molecular Immunology, Department of Surgery, University of Missouri School of Medicine , Columbia, MO 65212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L","family":"Franklin","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, University of Missouri , Columbia, MO 65201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron C","family":"Ericsson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, University of Missouri , Columbia, MO 65201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6746-4908","authenticated-orcid":false,"given":"Susan C","family":"McKarns","sequence":"additional","affiliation":[{"name":"Laboratory of TGF-\u03b2 Biology, Epigenetics, and Cytokine Regulation, Center for Cellular and Molecular Immunology, Department of Surgery, University of Missouri School of Medicine , Columbia, MO 65212"},{"name":"Department of Microbiology and Immunology, University of Missouri , Columbia, MO 65212"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"2025030704235160200_r1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1172\/JCI115102","article-title":"Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions","volume":"87","author":"Selmaj","year":"1991","journal-title":"J. Clin. Invest."},{"key":"2025030704235160200_r2","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.4049\/jimmunol.161.8.4437","article-title":"Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis","volume":"161","author":"Begolka","year":"1998","journal-title":"J. Immunol."},{"key":"2025030704235160200_r3","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/intimm\/2.6.539","article-title":"Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity","volume":"2","author":"Powell","year":"1990","journal-title":"Int. Immunol."},{"key":"2025030704235160200_r4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1212\/WNL.53.3.457","article-title":"TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study","volume":"53","author":"The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS\/MRI Analysis Group","year":"1999","journal-title":"Neurology"},{"key":"2025030704235160200_r5","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/nature03727","article-title":"Design of effective immunotherapy for human autoimmunity","volume":"435","author":"Feldmann","year":"2005","journal-title":"Nature"},{"key":"2025030704235160200_r6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jns.2007.08.004","article-title":"Endogenous or exogenous oligodendrocytes for remyelination","volume":"265","author":"Blakemore","year":"2008","journal-title":"J. Neurol. Sci."},{"key":"2025030704235160200_r7","first-page":"42","article-title":"Neuromyelitis optica","volume":"13","author":"Wingerchuk","year":"2006","journal-title":"Int. MS J."},{"key":"2025030704235160200_r8","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/nature07036","article-title":"Induction and effector functions of TH17 cells","volume":"453","author":"Bettelli","year":"2008","journal-title":"Nature"},{"key":"2025030704235160200_r9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbadis.2010.05.012","article-title":"Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis?","volume":"1812","author":"Lovett-Racke","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2025030704235160200_r10","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.4049\/jimmunol.161.9.4480","article-title":"B-cell-deficient mice develop experimental allergic encephalomyelitis with demyelination after myelin oligodendrocyte glycoprotein sensitization","volume":"161","author":"Hjelmstr\u00f6m","year":"1998","journal-title":"J. Immunol."},{"key":"2025030704235160200_r11","doi-asserted-by":"crossref","first-page":"3432","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3432::AID-IMMU3432>3.0.CO;2-2","article-title":"B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide","volume":"29","author":"Lyons","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025030704235160200_r12","doi-asserted-by":"crossref","first-page":"462","DOI":"10.4049\/jimmunol.171.1.462","article-title":"Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL\/6 mice","volume":"171","author":"Oliver","year":"2003","journal-title":"J. Immunol."},{"key":"2025030704235160200_r13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/ncpneuro0764","article-title":"Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica","volume":"4","author":"Jarius","year":"2008","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"2025030704235160200_r14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/ana.23651","article-title":"Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter","volume":"72","author":"Varrin-Doyer","year":"2012","journal-title":"Ann. Neurol."},{"key":"2025030704235160200_r15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40478-015-0207-1","article-title":"Pathogenic aquaporin-4 reactive T cells are sufficient to induce mouse model of neuromyelitis optica","volume":"3","author":"Jones","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"2025030704235160200_r16","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0962-8924(00)89088-1","article-title":"Two tumour necrosis factor receptors: structure and function","volume":"5","author":"Vandenabeele","year":"1995","journal-title":"Trends Cell Biol."},{"key":"2025030704235160200_r17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1365-2249.2011.04375.x","article-title":"The tumour necrosis factor\/TNF receptor superfamily: therapeutic targets in autoimmune diseases","volume":"164","author":"Vinay","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"2025030704235160200_r18","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nrd3030","article-title":"TNF receptor 2 pathway: drug target for autoimmune diseases","volume":"9","author":"Faustman","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"2025030704235160200_r19","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4049\/jimmunol.179.1.154","article-title":"Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells","volume":"179","author":"Chen","year":"2007","journal-title":"J. Immunol."},{"key":"2025030704235160200_r20","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/eji.200940022","article-title":"Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood","volume":"40","author":"Chen","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025030704235160200_r21","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nature11307","article-title":"TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis","volume":"488","author":"Gregory","year":"2012","journal-title":"Nature"},{"key":"2025030704235160200_r22","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/(SICI)1521-4141(199902)29:02<626::AID-IMMU626>3.0.CO;2-A","article-title":"Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1","volume":"29","author":"Eugster","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025030704235160200_r23","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.4049\/jimmunol.1300633","article-title":"Altered expression of oligodendrocyte and neuronal marker genes predicts the clinical onset of autoimmune encephalomyelitis and indicates the effectiveness of multiple sclerosis-directed therapeutics","volume":"192","author":"Evangelidou","year":"2014","journal-title":"J. Immunol."},{"key":"2025030704235160200_r24","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.4049\/jimmunol.169.9.4712","article-title":"Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis","volume":"169","author":"Kohm","year":"2002","journal-title":"J. Immunol."},{"key":"2025030704235160200_r25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/intimm\/dxh029","article-title":"IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells","volume":"16","author":"Zhang","year":"2004","journal-title":"Int. Immunol."},{"key":"2025030704235160200_r26","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.4049\/jimmunol.175.5.3025","article-title":"Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system","volume":"175","author":"McGeachy","year":"2005","journal-title":"J. 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Med."},{"key":"2025030704235160200_r33","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1172\/JCI28334","article-title":"Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice","volume":"116","author":"Bettelli","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025030704235160200_r34","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/ni1430","article-title":"CNS myeloid DCs presenting endogenous myelin peptides \u201cpreferentially\u201d polarize CD4+ TH-17 cells in relapsing EAE","volume":"8","author":"Bailey","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025030704235160200_r35","doi-asserted-by":"crossref","first-page":"808","DOI":"10.2144\/04365ST04","article-title":"Improved extraction of PCR-quality community DNA from digesta and fecal samples","volume":"36","author":"Yu","year":"2004","journal-title":"Biotechniques"},{"key":"2025030704235160200_r36","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1073\/pnas.1000080107","article-title":"Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample","volume":"108","author":"Caporaso","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030704235160200_r37","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/bioinformatics\/btr087","article-title":"PrimerProspector: de novo design and taxonomic analysis of barcoded polymerase chain reaction primers","volume":"27","author":"Walters","year":"2011","journal-title":"Bioinformatics"},{"key":"2025030704235160200_r38","doi-asserted-by":"crossref","first-page":"D800","DOI":"10.1093\/nar\/gkl856","article-title":"probeBase\u2014an online resource for rRNA-targeted oligonucleotide probes: new features 2007","volume":"35","author":"Loy","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2025030704235160200_r39","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Mago\u010d","year":"2011","journal-title":"Bioinformatics"},{"key":"2025030704235160200_r40","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1007s36","article-title":"Using QIIME to analyze 16S rRNA gene sequences from microbial communities","volume-title":"Curr. Protoc. Bioinformatics Chapter 10","author":"Kuczynski","year":"2011"},{"key":"2025030704235160200_r41","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2025030704235160200_r42","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/AEM.03006-05","article-title":"Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB","volume":"72","author":"DeSantis","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"2025030704235160200_r43","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.4049\/jimmunol.1500286","article-title":"Transmembrane TNF-TNFR2 impairs Th17 differentiation by promoting Il2 expression","volume":"195","author":"Miller","year":"2015","journal-title":"J. Immunol."},{"key":"2025030704235160200_r44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1006\/cimm.2000.1706","article-title":"Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG35\u201355-induced experimental autoimmune encephalomyelitis","volume":"205","author":"Suvannavejh","year":"2000","journal-title":"Cell. Immunol."},{"key":"2025030704235160200_r45","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1084\/jem.193.4.427","article-title":"Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: implications for pathogenesis and therapy of autoimmune demyelination","volume":"193","author":"Kassiotis","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025030704235160200_r46","doi-asserted-by":"crossref","first-page":"e90117","DOI":"10.1371\/journal.pone.0090117","article-title":"Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis","volume":"9","author":"Williams","year":"2014","journal-title":"PLoS One"},{"key":"2025030704235160200_r47","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1172\/JCI28330","article-title":"Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell\/B cell cooperation","volume":"116","author":"Krishnamoorthy","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025030704235160200_r48","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.181.2.1272","article-title":"Biphasic regulation of Il2 transcription in CD4+ T cells: roles for TNF-\u03b1 receptor signaling and chromatin structure","volume":"181","author":"McKarns","year":"2008","journal-title":"J. Immunol."},{"key":"2025030704235160200_r49","first-page":"355","article-title":"Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system","volume":"76","author":"Berger","year":"1997","journal-title":"Lab. Invest."},{"key":"2025030704235160200_r50","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1136\/jnnp.60.4.382","article-title":"Clinical, CSF, and MRI findings in Devic\u2019s neuromyelitis optica","volume":"60","author":"O\u2019Riordan","year":"1996","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"2025030704235160200_r51","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fmicb.2011.00148","article-title":"The starting lineup: key microbial players in intestinal immunity and homeostasis","volume":"2","author":"Reading","year":"2011","journal-title":"Front. Microbiol."},{"key":"2025030704235160200_r52","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1002\/1529-0131(200109)44:9<1977::AID-ART345>3.0.CO;2-6","article-title":"Demyelinating and neurologic events reported in association with tumor necrosis factor alpha antagonism: by what mechanisms could tumor necrosis factor alpha antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis?","volume":"44","author":"Robinson","year":"2001","journal-title":"Arthritis Rheum."},{"key":"2025030704235160200_r53","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.nbd.2004.07.015","article-title":"Genes, environment, and susceptibility to multiple sclerosis","volume":"17","author":"Sotgiu","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"2025030704235160200_r54","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1001\/archneurol.2009.49","article-title":"A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis","volume":"66","author":"Rovira","year":"2009","journal-title":"Arch. Neurol."},{"key":"2025030704235160200_r55","doi-asserted-by":"crossref","first-page":"460825","DOI":"10.1155\/2012\/460825","article-title":"Neuromyelitis optica: an antibody-mediated disorder of the central nervous system","volume":"2012","author":"Oh","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"2025030704235160200_r56","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1172\/JCI78082","article-title":"Sexual dimorphism in autoimmunity","volume":"125","author":"Rubtsova","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2025030704235160200_r57","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1172\/JCI73408","article-title":"Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility","volume":"124","author":"Cruz-Orengo","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025030704235160200_r58","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/ATVBAHA.109.197582","article-title":"Claudin-5 as a novel estrogen target in vascular endothelium","volume":"30","author":"Burek","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2025030704235160200_r59","doi-asserted-by":"crossref","first-page":"9979","DOI":"10.1073\/pnas.95.17.9979","article-title":"Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases","volume":"95","author":"Becker","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030704235160200_r60","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","article-title":"Variation in the human immune system is largely driven by non-heritable influences","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"key":"2025030704235160200_r61","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1084\/jem.20090299","article-title":"Spontaneous relapsing-remitting EAE in the SJL\/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells","volume":"206","author":"P\u00f6llinger","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025030704235160200_r62","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.1233521","article-title":"Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity","volume":"339","author":"Markle","year":"2013","journal-title":"Science"},{"key":"2025030704235160200_r63","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.immuni.2013.08.013","article-title":"Gender bias in autoimmunity is influenced by microbiota","volume":"39","author":"Yurkovetskiy","year":"2013","journal-title":"Immunity"},{"key":"2025030704235160200_r64","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1056\/NEJM200008173430707","article-title":"Epstein-Barr virus infection","volume":"343","author":"Cohen","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2025030704235160200_r65","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/ana.20820","article-title":"Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis","volume":"59","author":"Thacker","year":"2006","journal-title":"Ann. Neurol."},{"key":"2025030704235160200_r66","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1128\/JCM.02532-05","article-title":"Molecular mimicry revisited: gut bacteria and multiple sclerosis","volume":"44","author":"Westall","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"2025030704235160200_r67","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00401-012-0949-9","article-title":"Commensal gut flora and brain autoimmunity: a love or hate affair?","volume":"123","author":"Berer","year":"2012","journal-title":"Acta Neuropathol."},{"key":"2025030704235160200_r68","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cell.2005.05.007","article-title":"An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system","volume":"122","author":"Mazmanian","year":"2005","journal-title":"Cell"},{"key":"2025030704235160200_r69","doi-asserted-by":"crossref","first-page":"4432","DOI":"10.1038\/ncomms5432","article-title":"An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling","volume":"5","author":"Wang","year":"2014","journal-title":"Nat. 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Natl. Acad. Sci. 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Gastroenterol. Hepatol."},{"key":"2025030704235160200_r88","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1038\/nutd.2015.9","article-title":"Specific gut microbiota features and metabolic markers in postmenopausal women with obesity","volume":"5","author":"Brahe","year":"2015","journal-title":"Nutr. Diabetes"},{"key":"2025030704235160200_r89","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.4049\/jimmunol.179.10.6604","article-title":"Molecular mimics can induce novel self peptide-reactive CD4+ T cell clonotypes in autoimmune disease","volume":"179","author":"Ercolini","year":"2007","journal-title":"J. Immunol."},{"key":"2025030704235160200_r90","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.4049\/jimmunol.169.10.5415","article-title":"Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs","volume":"169","author":"de Vos","year":"2002","journal-title":"J. Immunol."},{"key":"2025030704235160200_r91","doi-asserted-by":"crossref","first-page":"12204","DOI":"10.1073\/pnas.0909122107","article-title":"Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota","volume":"107","author":"Round","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030704235160200_r92","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1586\/14760584.7.8.1155","article-title":"Specific Lactobacillus species differentially activate Toll-like receptors and downstream signals in dendritic cells","volume":"7","author":"Mohamadzadeh","year":"2008","journal-title":"Expert Rev. Vaccines"},{"key":"2025030704235160200_r93","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1038\/nm.2505","article-title":"Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut","volume":"17","author":"Shulzhenko","year":"2011","journal-title":"Nat. Med."},{"key":"2025030704235160200_r94","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.4049\/jimmunol.146.12.4362","article-title":"Estrogen regulates the IFN-gamma promoter","volume":"146","author":"Fox","year":"1991","journal-title":"J. Immunol."},{"key":"2025030704235160200_r95","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.4049\/jimmunol.159.3.1150","article-title":"The effects of IFN-\u03b3 on CD40-mediated activation of B cells from X-linked immunodeficient or normal mice","volume":"159","author":"Johnson-L\u00e9ger","year":"1997","journal-title":"J. Immunol."},{"key":"2025030704235160200_r96","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev.iy.08.040190.001511","article-title":"Lymphokine control of in vivo immunoglobulin isotype selection","volume":"8","author":"Finkelman","year":"1990","journal-title":"Annu. Rev. 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Rheumatol."},{"key":"2025030704235160200_r99","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1136\/ard.2010.139212","article-title":"Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial","volume":"70","author":"Saevarsdottir","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"2025030704235160200_r100","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1136\/ard.2007.084897","article-title":"Sex: a major predictor of remission as measured by 28-joint Disease Activity Score (DAS28) in early rheumatoid arthritis?","volume":"67","author":"M\u00e4kinen","year":"2008","journal-title":"Ann. Rheum. 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