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Theiler\u2019s murine encephalomyelitis virus (TMEV) infection in SJL\/J mice has been widely used as a viral model of MS, since TMEV-infected mice develop MS-like demyelination and axonal degeneration with viral persistence in the CNS. In the TMEV model, we previously demonstrated upregulation of immunoglobulin (Ig) A-related genes in the CNS, as well as IgA deposition and IgA-positive cell infiltration in demyelinating lesions. Although IgA has been implicated in the pathophysiology of MS, its precise role remains unclear. To determine the role of IgA in the TMEV model, we established IgA knockout (KO) mice on the SJL\/J background; IgA KO mice lacked serum IgA and exhibited altered gut microbiota compositions. We found that TMEV-infected IgA KO mice developed more severe neurological signs than wild-type (WT) mice. IgA KO mice also had more severe inflammatory demyelination with higher levels of viral persistence and T cell infiltration in the CNS than WT mice. Immunologically, IgA KO mice mounted TMEV-specific lymphoproliferative responses and serum anti-viral antibody isotype titers, except for IgA, which were comparable to WT mice. Interleukin (IL)-17 and IL-10 productions were higher in IgA KO mice than in WT mice. Thus, IgA could play a protective role in the TMEV model in WT mice; IgA deficiency-mediated gut dysbiosis may contribute to enhanced immunopathology in IgA KO mice.<\/jats:p>","DOI":"10.3390\/cells15181665","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:32:01Z","timestamp":1789468321000},"page":"1665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IgA Deficiency Exacerbates an Animal Model of Multiple Sclerosis Induced with Theiler\u2019s Virus"],"prefix":"10.3390","volume":"15","author":[{"given":"Fumitaka","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo A.","family":"Hinay Jr.","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4619-9345","authenticated-orcid":false,"given":"Seiichi","family":"Omura","sequence":"additional","affiliation":[{"name":"Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa 649-6493, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-815X","authenticated-orcid":false,"given":"Ijaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Tropical Viral Vaccine Development, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8064-3625","authenticated-orcid":false,"given":"Sandesh","family":"Rimal","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah-Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Arts and Sciences, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reona","family":"Shiro","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiyo","family":"Tsuji-Kawahara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-714X","authenticated-orcid":false,"given":"Ikuo","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kindai University, Sakai 590-0197, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1056\/NEJM199801293380502","article-title":"Axonal transection in the lesions of multiple sclerosis","volume":"338","author":"Trapp","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00401-013-1082-0","article-title":"Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons","volume":"125","author":"Singh","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cell.2025.12.031","article-title":"Myelin antigen capture in the CNS by B cells expressing EBV latent membrane protein 1 leads to demyelinating lesion formation","volume":"189","author":"Kim","year":"2026","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q","article-title":"Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination","volume":"47","author":"Lucchinetti","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/1531-8249(199901)45:1<33::AID-ART7>3.0.CO;2-G","article-title":"Isolation of myelin basic protein-specific T cells predominantly from the memory T-cell compartment in multiple sclerosis","volume":"45","author":"Burns","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s13311-020-00975-7","article-title":"Differential effects of fingolimod and natalizumab on B cell repertoires in multiple sclerosis patients","volume":"18","author":"Kowarik","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2207291120","DOI":"10.1073\/pnas.2207291120","article-title":"Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity","volume":"120","author":"Shinoda","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106886","DOI":"10.1016\/j.msard.2025.106886","article-title":"Six-year safety and efficacy outcomes with first-line ofatumumab in recently diagnosed treatment-naive patients with relapsing multiple sclerosis","volume":"105","author":"Hauser","year":"2026","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/NEN.0b013e3181e332ec","article-title":"Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: Implications for viral persistence and intrathecal B-cell activation","volume":"69","author":"Serafini","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1093\/brain\/awh390","article-title":"Early and late HHV-6 gene transcripts in multiple sclerosis lesions and normal appearing white matter","volume":"128","author":"Opsahl","year":"2005","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-022-04432-7","article-title":"Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM","volume":"603","author":"Lanz","year":"2022","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pneurobio.2012.11.003","article-title":"Viral models of multiple sclerosis: Neurodegeneration and demyelination in mice infected with Theiler\u2019s virus","volume":"101\u2013102","author":"Mecha","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24464","DOI":"10.1073\/pnas.2007814117","article-title":"Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection","volume":"117","author":"Sariol","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sato, F., Nakamura, Y., Katsuki, A., Khadka, S., Ahmad, I., Omura, S., Martinez, N.E., and Tsunoda, I. (2022). Curdlan, a microbial \u03b2-glucan, has contrasting effects on autoimmune and viral models of multiple sclerosis. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.805302"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2350452","DOI":"10.1002\/eji.202350452","article-title":"Chronic encephalomyelitis virus exhibits cellular tropism and evades pDCs by binding to sialylated integrins as the cell surface receptors","volume":"53","author":"Takeda","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1128\/jvi.61.5.1507-1516.1987","article-title":"Analysis of the complete nucleotide sequence of the picornavirus Theiler\u2019s murine encephalomyelitis virus indicates that it is closely related to cardioviruses","volume":"61","author":"Pevear","year":"1987","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1128\/jvi.63.5.2081-2087.1989","article-title":"Survival of athymic (nu\/nu) mice after Theiler\u2019s murine encephalomyelitis virus infection by passive administration of neutralizing monoclonal antibody","volume":"63","author":"Fujinami","year":"1989","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"919","DOI":"10.4049\/jimmunol.152.2.919","article-title":"Class II-restricted T cell responses in Theiler\u2019s murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope","volume":"152","author":"Gerety","year":"1994","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1099\/0022-1317-68-6-1659","article-title":"The effect of L3T4 T cell depletion on the pathogenesis of Theiler\u2019s murine encephalomyelitis virus infection in CBA mice","volume":"68","author":"Welsh","year":"1987","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bbi.2014.07.008","article-title":"Th17-biased ROR\u03b3t transgenic mice become susceptible to a viral model for multiple sclerosis","volume":"43","author":"Martinez","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1084\/jem.20082030","article-title":"Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection","volume":"206","author":"Hou","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1084\/jem.171.6.1893","article-title":"Monoclonal antibody to Theiler\u2019s murine encephalomyelitis virus defines a determinant on myelin and oligodendrocytes, and augments demyelination in experimental allergic encephalomyelitis","volume":"171","author":"Yamada","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41577-019-0261-1","article-title":"Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA","volume":"20","author":"Chen","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Omura, S., Sato, F., Park, A.-M., Fujita, M., Khadka, S., Nakamura, Y., Katsuki, A., Nishio, K., Gavins, F.N.E., and Tsunoda, I. (2020). Bioinformatics analysis of gut microbiota and CNS transcriptome in virus-induced acute myelitis and chronic inflammatory demyelination; potential association of distinct bacteria with CNS IgA upregulation. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01138"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4049\/jimmunol.126.1.27","article-title":"Immunoglobulins in the cerebrospinal fluid: Changes during acute viral encephalitis in mice","volume":"126","author":"Griffin","year":"1981","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0165-5728(87)90015-4","article-title":"Changes in cerebrospinal fluid cells, IgG and IgA during herpes simplex virus encephalitis in rabbits","volume":"14","author":"Laskin","year":"1987","journal-title":"J. Neuroimmunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/BF00868395","article-title":"Intrathecal production of specific IgA antibodies in CNS infections","volume":"242","author":"Roberg","year":"1995","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1084\/jem.20180427","article-title":"IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria","volume":"215","author":"Nakajima","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nri.2017.7","article-title":"Dysbiosis and the immune system","volume":"17","author":"Levy","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gutjnl-2020-322873","article-title":"Immunoglobulin A-specific deficiency induces spontaneous inflammation specifically in the ileum","volume":"71","author":"Nagaishi","year":"2022","journal-title":"Gut"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2018.11.035","article-title":"Recirculating intestinal IgA-producing cells regulate neuroinflammation via IL-10","volume":"176","author":"Rojas","year":"2019","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eabc7191","DOI":"10.1126\/sciimmunol.abc7191","article-title":"Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis","volume":"5","author":"Zhou","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1001\/archneur.1971.00490040052007","article-title":"Immunoglobulins in multiple sclerosis and infections of the nervous system","volume":"25","author":"Link","year":"1971","journal-title":"Arch. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ymeth.2020.04.007","article-title":"Efficient production of large deletion and gene fragment knock-in mice mediated by genome editing with Cas9-mouse Cdt1 in mouse zygotes","volume":"191","author":"Ayabe","year":"2021","journal-title":"Methods"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ahmad, I., Omura, S., Khadka, S., Sato, F., Park, A.-M., Nguyen, C.T., Rimal, S., Fukase, K., Shimoyama, A., and Tsunoda, I. (2026). The safety of Alcaligenes lipid A in a virus-induced immune disease model associated with IgA, Th17 cells, and microbiota. Viruses, 18.","DOI":"10.3390\/v18020155"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Khadka, S., Omura, S., Sato, F., and Tsunoda, I. (2023). Adjuvant injections altered the ileal and fecal microbiota differently with changes in immunoglobulin isotypes and antimycobacterial antibody responses. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032818"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s00705-018-3729-6","article-title":"Immunoregulation of Theiler\u2019s virus-induced demyelinating disease by glatiramer acetate without suppression of antiviral immune responses","volume":"163","author":"Omura","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Khadka, S., Omura, S., Sato, F., Nishio, K., Kakeya, H., and Tsunoda, I. (2021). Curcumin \u03b2-D-glucuronide modulates an autoimmune model of multiple sclerosis with altered gut microbiota in the ileum and feces. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.772962"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ahmad, I., Omura, S., Sato, F., Park, A.-M., Khadka, S., Gavins, F.N.E., Tanaka, H., Kimura, M.Y., and Tsunoda, I. (2024). Exploring the role of platelets in virus-induced inflammatory demyelinating disease and myocarditis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063460"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10496","DOI":"10.1038\/s41598-017-10980-0","article-title":"T-bet, but not Gata3, overexpression is detrimental in a neurotropic viral infection","volume":"7","author":"Sato","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1128\/jvi.53.2.651-657.1985","article-title":"Neutralizing monoclonal antibodies to Theiler\u2019s murine encephalomyelitis viruses","volume":"53","author":"Nitayaphan","year":"1985","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1128\/jvi.57.3.992-997.1986","article-title":"Demyelinating lesions due to Theiler\u2019s virus are associated with ongoing central nervous system infection","volume":"57","author":"Chamorro","year":"1986","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nm0298-187","article-title":"Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis","volume":"4","author":"McGavern","year":"1998","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11481-009-9179-x","article-title":"Neuropathogenesis of Theiler\u2019s murine encephalomyelitis virus infection, an animal model for multiple sclerosis","volume":"5","author":"Tsunoda","year":"2010","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.3390\/ijms15021700","article-title":"Regulation of an autoimmune model for multiple sclerosis in Th2-biased GATA3 transgenic mice","volume":"15","author":"Fernando","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.nrl.2011.08.004","article-title":"Selective immunoglobulin A deficiency is exceptionally associated with multiple sclerosis","volume":"27","author":"Pereira","year":"2012","journal-title":"Neurolog\u00eda"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e947678","DOI":"10.12659\/AJCR.947678","article-title":"Selective IgA deficiency complicated with pernicious anemia diagnosed after febrile non-hemolytic transfusion reaction","volume":"26","author":"Yoshino","year":"2025","journal-title":"Am. J. Case Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.nrl.2010.12.012","article-title":"Selective IgA deficiency and multiple sclerosis","volume":"26","author":"Patrucco","year":"2011","journal-title":"Neurolog\u00eda"},{"key":"ref_50","first-page":"1122","article-title":"A case of multiple sclerosis demonstrating ossification of anterior, posterior longitudinal ligament, thickening of the skull, and selective IgA deficiency","volume":"27","author":"Iwasaki","year":"1987","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1053\/j.gastro.2021.02.053","article-title":"Gut microbiota perturbation in IgA deficiency is influenced by IgA-autoantibody status","volume":"160","author":"Moll","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13574","DOI":"10.1038\/s41598-019-49923-2","article-title":"IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM","volume":"9","author":"Catanzaro","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eade2335","DOI":"10.1126\/sciimmunol.ade2335","article-title":"IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation","volume":"8","author":"Conrey","year":"2023","journal-title":"Sci. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41522-024-00597-3","article-title":"Large-scale metagenomic assembly provide new insights into the genetic evolution of gut microbiomes in plateau ungulates","volume":"10","author":"Xu","year":"2024","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Smith, B.J., Miller, R.A., Ericsson, A.C., Harrison, D.C., Strong, R., and Schmidt, T.M. (2019). Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1494-7"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e10941","DOI":"10.7717\/peerj.10941","article-title":"Extensive microbial diversity within the chicken gut microbiome revealed by metagenomics and culture","volume":"9","author":"Gilroy","year":"2021","journal-title":"PeerJ"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10109","DOI":"10.1038\/s41598-024-59148-7","article-title":"Genome plasticity shapes the ecology and evolution of Phocaeicola dorei and Phocaeicola vulgatus","volume":"14","author":"Grimaud","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1038\/s41598-017-02995-4","article-title":"Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1038\/s41467-024-47683-w","article-title":"Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer\u2019s disease mouse models","volume":"15","author":"Beauchamp","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Omenetti, S., and Pizarro, T.T. (2015). The Treg\/Th17 axis: A dynamic balance regulated by the gut microbiome. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00639"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1128\/JVI.03395-12","article-title":"Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection","volume":"87","author":"Zhang","year":"2013","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.4049\/jimmunol.155.9.4497","article-title":"Treatment with bacterial LPS renders genetically resistant C57BL\/6 mice susceptible to Theiler\u2019s virus-induced demyelinating disease","volume":"155","author":"Pullen","year":"1995","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0002-9440(10)63922-3","article-title":"Axonal injury heralds virus-induced demyelination","volume":"162","author":"Tsunoda","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1658936","article-title":"Antibody-mediated clearance of alphavirus infection from neurons","volume":"254","author":"Levine","year":"1991","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7286","DOI":"10.1128\/jvi.69.11.7286-7290.1995","article-title":"Gamma interferon is critical for resistance to Theiler\u2019s virus-induced demyelination","volume":"69","author":"Rodriguez","year":"1995","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0165-5728(94)90004-3","article-title":"Alteration in the level of interferon-\u03b3 results in acceleration of Theiler\u2019s virus-induced demyelinating disease","volume":"55","author":"Pullen","year":"1994","journal-title":"J. Neuroimmunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5586","DOI":"10.4049\/jimmunol.161.10.5586","article-title":"Suppressive effect on Theiler\u2019s murine encephalomyelitis virus-induced demyelinating disease by the administration of anti-IL-12 antibody","volume":"161","author":"Inoue","year":"1998","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/bpa.12119","article-title":"Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis","volume":"24","author":"Martinez","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Uhde, A.-K., Herder, V., Akram Khan, M., Ciurkiewicz, M., Schaudien, D., Teich, R., Floess, S., Baumg\u00e4rtner, W., Huehn, J., and Beineke, A. (2016). Viral infection of the central nervous system exacerbates interleukin-10 receptor deficiency-mediated colitis in SJL mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161883"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/ibd\/izy318","article-title":"An increased abundance of Clostridiaceae characterizes arthritis in inflammatory bowel disease and rheumatoid arthritis: A cross-sectional study","volume":"25","author":"Chen","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature07540","article-title":"A core gut microbiome in obese and lean twins","volume":"457","author":"Turnbaugh","year":"2009","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., Chihara, N., Tomita, A., Sato, W., and Kim, S.-W. (2015). Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137429"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"578696","DOI":"10.1016\/j.jneuroim.2025.578696","article-title":"Gut dysbiosis influences the pathophysiology of multiple sclerosis: A case-control study from North India","volume":"407","author":"Kaur","year":"2025","journal-title":"J. Neuroimmunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1665\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:29:00Z","timestamp":1789619340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/18\/1665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":73,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15181665"],"URL":"https:\/\/doi.org\/10.3390\/cells15181665","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}