{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:13:02Z","timestamp":1773414782251,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"publisher","award":["K08 T26-1616-11"],"award-info":[{"award-number":["K08 T26-1616-11"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"publisher","award":["U01 AA016651"],"award-info":[{"award-number":["U01 AA016651"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"NIAAA","doi-asserted-by":"publisher","award":["T32 AA007471"],"award-info":[{"award-number":["T32 AA007471"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institutional Dell Medical School Startup Funds"},{"name":"Homer Lindsey Bruce & Fred Murphy Jones Endowed Fellowship"},{"name":"NIH Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship","award":["F31 AA032720"],"award-info":[{"award-number":["F31 AA032720"]}]},{"DOI":"10.13039\/100000026","name":"NIDA","doi-asserted-by":"publisher","award":["5T32 DA018926-18"],"award-info":[{"award-number":["5T32 DA018926-18"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The University of Texas at Austin Graduate Continuing Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Both epidemiological studies and prior work in animal models suggest that moderate-dose alcohol reduces disease severity across several autoimmune conditions, including multiple sclerosis (MS). However, the mechanisms underlying the potentially beneficial effects of alcohol and how these effects may change with alcohol dose in autoimmunity remain underexplored. In this study, we characterize the effects of chronic, high-dose ethanol consumption in experimental autoimmune encephalomyelitis (EAE), a murine model of MS, by examining EAE disease severity, gut microbial composition, and peripheral cell immunophenotypes. We found that high-dose ethanol-fed males exhibited a significant amelioration in peak EAE disease severity, in association with decreased T cell activation and B cell proportions. Concurrently, we observed proinflammatory shifts in gut microbiota and hepatic lipid accumulation. Our results suggest that high dose ethanol may benefit autoimmune neuroinflammation in EAE through immunosuppressive effects on adaptive immunity, however its toxic systemic effects preclude the use of alcohol as an immunomodulator in MS. Overall, our findings reveal a mechanistic basis for alcohol\u2019s beneficial properties in autoimmunity and could inform the development of more targeted disease modifying therapies that recapitulate these benefits without alcohol-associated toxicity.<\/jats:p>","DOI":"10.3390\/biom16030427","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:26:19Z","timestamp":1773390379000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-0135","authenticated-orcid":false,"given":"Adriana S. P.","family":"Nuncio","sequence":"first","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Motovilov","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9190-3626","authenticated-orcid":false,"given":"Max","family":"Weed","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5951-9243","authenticated-orcid":false,"given":"Sam","family":"Bazzi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"University of Texas Southwestern (UTSW) Medical School, UTSW Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esha","family":"Idnani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6687-7303","authenticated-orcid":false,"given":"Turner","family":"Lime","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4222-4911","authenticated-orcid":false,"given":"Daniela Carrizales","family":"Sauceda","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4499-6183","authenticated-orcid":false,"given":"Regina A.","family":"Mangieri","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-9762","authenticated-orcid":false,"given":"Cole","family":"Maguire","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-3591","authenticated-orcid":false,"given":"Esther","family":"Melamed","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA"},{"name":"Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41582-021-00556-y","article-title":"Apparent changes in the epidemiology and severity of multiple sclerosis","volume":"17","author":"Magyari","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028944","DOI":"10.1101\/cshperspect.a028944","article-title":"Lifestyle and Environmental Factors in Multiple Sclerosis","volume":"9","author":"Alfredsson","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1080\/14737175.2021.1978843","article-title":"Role of environmental factors in multiple sclerosis","volume":"21","author":"Zarghami","year":"2021","journal-title":"Expert Rev. Neurother."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ghezzi, L., Cantoni, C., Pinget, G.V., Zhou, Y., and Piccio, L. (2021). Targeting the gut to treat multiple sclerosis. J. Clin. Investig., 131.","DOI":"10.1172\/JCI143774"},{"key":"ref_5","first-page":"1","article-title":"Microbiota-immune interactions: From gut to brain","volume":"7","author":"Stokes","year":"2020","journal-title":"LymphoSign J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marano, G., Mazza, M., Lisci, F.M., Ciliberto, M., Traversi, G., Kotzalidis, G.D., De Berardis, D., Laterza, L., Sani, G., and Gasbarrini, A. (2023). The Microbiota\u2013Gut\u2013Brain Axis: Psychoneuroimmunological Insights. Nutrients, 15.","DOI":"10.3390\/nu15061496"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.apmr.2008.11.017","article-title":"Alcohol Misuse and Multiple Sclerosis","volume":"90","author":"Turner","year":"2009","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jns.2013.12.029","article-title":"Alcohol and substance use in multiple sclerosis","volume":"338","author":"Beier","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1017\/S0007114507838049","article-title":"Moderate alcohol consumption and the immune system: A review","volume":"98","author":"Romeo","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0162-3109(95)00032-4","article-title":"Different pathways of in vitro ethanol-induced apoptosis in thymocytes and splenic T and B lymphocytes","volume":"31","author":"Slukvin","year":"1995","journal-title":"Immunopharmacology"},{"key":"ref_11","first-page":"41","article-title":"BIOCHEMICAL AND GENETIC STUDIES ON ENZYMES OF ALCOHOL METABOLISM: THE MOUSE AS A MODEL ORGANISM FOR HUMAN STUDIES","volume":"21","author":"Holmes","year":"1986","journal-title":"Alcohol Alcohol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/glia.22835","article-title":"Transient activation of microglia following acute alcohol exposure in developing mouse neocortex is primarily driven by BAX-dependent neurodegeneration","volume":"63","author":"Ahlers","year":"2015","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1916278","DOI":"10.1080\/19490976.2021.1916278","article-title":"Alcohol as friend or foe in autoimmune diseases: A role for gut microbiome?","volume":"13","author":"Caslin","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/acer.15049","article-title":"The vicious cycle between (neuro)inflammation and alcohol use disorder: An opportunity to develop new medications?","volume":"47","author":"Ray","year":"2023","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"147","DOI":"10.35946\/arcr.v38.2.01","article-title":"Alcoholic Liver Disease: Pathogenesis and Current Management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nowak, A.J., and Relja, B. (2020). The Impact of Acute or Chronic Alcohol Intake on the NF-\u03baB Signaling Pathway in Alcohol-Related Liver Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249407"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25808","DOI":"10.1073\/pnas.1912359116","article-title":"Alcohol shifts gut microbial networks and ameliorates a murine model of neuroinflammation in a sex-specific pattern","volume":"116","author":"Caslin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-15855-z","article-title":"Ethanol consumption inhibits TFH cell responses and the development of autoimmune arthritis","volume":"11","author":"Azizov","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/acr.23847","article-title":"Changes in Alcohol Use and Associations with Disease Activity, Health Status, and Mortality in Rheumatoid Arthritis","volume":"72","author":"Baker","year":"2019","journal-title":"Arthritis Care Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1007\/s10067-008-1004-z","article-title":"Moderate alcohol drinking might be protective for systemic lupus erythematosus: A systematic review and meta-analysis","volume":"27","author":"Wang","year":"2008","journal-title":"Clin. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1001\/jamaneurol.2013.5858","article-title":"Alcohol as a Modifiable Lifestyle Factor Affecting Multiple Sclerosis Risk","volume":"71","author":"Hillert","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000338920","article-title":"Alcohol Consumption as a Risk Factor for Autoimmune Thyroid Disease: A Prospective Study","volume":"1","author":"Effraimidis","year":"2012","journal-title":"Eur. Thyroid. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.msard.2017.06.011","article-title":"The effect of alcohol and red wine consumption on clinical and MRI outcomes in multiple sclerosis","volume":"17","author":"Chua","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pnpbp.2015.06.013","article-title":"The role of the gut\u2013brain axis in alcohol use disorders","volume":"65","author":"Gorky","year":"2016","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khan, M.A.S., and Chang, S.L. (2023). Alcohol and the Brain\u2013Gut Axis: The Involvement of Microglia and Enteric Glia in the Process of Neuro-Enteric Inflammation. Cells, 12.","DOI":"10.3390\/cells12202475"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"687745","DOI":"10.3389\/fgene.2021.687745","article-title":"Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases\u2014Evidence from a Large-Scale Genetic Analysis Totaling 1 Million Individuals","volume":"12","author":"Jiang","year":"2021","journal-title":"Front. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nprot.2013.032","article-title":"Mouse model of chronic and binge ethanol feeding (the NIAAA model)","volume":"8","author":"Bertola","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_28","first-page":"4142","article-title":"Microdialysis of Ethanol during Operant Ethanol Self-Administration and Ethanol Determination by Gas Chromatography","volume":"67","author":"Schier","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_29","unstructured":"(2026, February 02). Available online: https:\/\/hookelabs.com\/protocols\/eaeAI_C57BL6.html."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102466","DOI":"10.1016\/j.xpro.2023.102466","article-title":"Automated qualitative batch measurement of lipid droplets in the liver of bird using ImageJ","volume":"4","author":"Nishad","year":"2023","journal-title":"STAR Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/bioinformatics\/btx754","article-title":"bioBakery: A meta\u2019omic analysis environment","volume":"34","author":"McIver","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e65088","DOI":"10.7554\/eLife.65088","article-title":"Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3","volume":"10","author":"Beghini","year":"2021","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1111\/j.1530-0277.2011.01434.x","article-title":"Chronic Ethanol Consumption in Mice Alters Hepatocyte Lipid Droplet Properties","volume":"35","author":"Orlicky","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1111\/j.1530-0277.2010.01283.x","article-title":"1H and 31P NMR Lipidome of Ethanol-Induced Fatty Liver","volume":"34","author":"Fernando","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","article-title":"Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)","volume":"164","author":"Constantinescu","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jcmgh.2022.10.002","article-title":"Ethanol and its Nonoxidative Metabolites Promote Acute Liver Injury by Inducing ER Stress, Adipocyte Death, and Lipolysis","volume":"15","author":"Park","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ruiter-Lopez, L., Khan, M.A.S., Wang, X., and Song, B.-J. (2025). Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage. Antioxidants, 14.","DOI":"10.3390\/antiox14030302"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1053\/gast.2002.33613","article-title":"Alcohol and mitochondria: A dysfunctional relationship","volume":"122","author":"Hoek","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112196","DOI":"10.1016\/j.bbr.2019.112196","article-title":"Meta-analysis of alcohol induced gut dysbiosis and the resulting behavioral impact","volume":"376","author":"Qamar","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jhep.2013.01.035","article-title":"Alcohol and toxicity","volume":"59","author":"Rusyn","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Stojanov, S., Berlec, A., and \u0160trukelj, B. (2020). The Influence of Probiotics on the Firmicutes\/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111715"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"114892","DOI":"10.1016\/j.biopha.2023.114892","article-title":"The F\/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin","volume":"163","author":"Petakh","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Magne, F., Gotteland, M., Gauthier, L., Zazueta, A., Pesoa, S., Navarrete, P., and Balamurugan, R. (2020). The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?. Nutrients, 12.","DOI":"10.3390\/nu12051474"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The Gut Microbiota as an Environmental Factor That Regulates Fat Storage","volume":"101","author":"Ding","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E4485","DOI":"10.1073\/pnas.1415174111","article-title":"Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity","volume":"111","author":"Leclercq","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/s41423-025-01326-2","article-title":"The gut microbiota in cancer immunity and immunotherapy","volume":"22","author":"Xie","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1084\/jem.20020029","article-title":"The Immune Regulatory Function of Lymphoproliferative Double Negative T Cells In Vitro and In Vivo","volume":"196","author":"Ford","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/eji.201040982","article-title":"Characterization of the immunoregulatory function of human TCR-\u03b1\u03b2+ CD4\u2212CD8\u2212 double-negative T cells","volume":"41","author":"Voelkl","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7072","DOI":"10.1038\/s41467-025-62089-y","article-title":"Intestinal CD4\u2212CD8\u03b1\u03b2\u2212TCR\u03b1\u03b2+ T cells function as tolerogenic antigen presenting cells in mice","volume":"16","author":"Nemoto","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Melamed, E., Palmer, J.L., and Fonken, C. (2022). Advantages and limitations of experimental autoimmune encephalomyelitis in breaking down the role of the gut microbiome in multiple sclerosis. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1019877"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0074-7742(07)79003-7","article-title":"The Role of CD4 T Cells in the Pathogenesis of Multiple Sclerosis","volume":"79","author":"Chitnis","year":"2007","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"eadp8109","DOI":"10.1126\/scitranslmed.adp8109","article-title":"Tissue-resident memory CD4+ T cells infiltrate the CNS in progressive multiple sclerosis and contribute to chronic autoimmunity in mice","volume":"17","author":"Pignata","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_54","first-page":"3420","article-title":"Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression","volume":"118","author":"Matsushita","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cell.2018.08.011","article-title":"Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis","volume":"175","author":"Jelcic","year":"2018","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Michel, L., Touil, H., Pikor, N.B., Gommerman, J.L., Prat, A., and Bar-Or, A. (2015). B Cells in the Multiple Sclerosis Central Nervous System: Trafficking and Contribution to CNS-Compartmentalized Inflammation. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00636"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4049\/jimmunol.1302171","article-title":"B Cells Promote Induction of Experimental Autoimmune Encephalomyelitis by Facilitating Reactivation of T Cells in the Central Nervous System","volume":"192","author":"Pierson","year":"2014","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ana.25119","article-title":"B-cell Therapy for Multiple Sclerosis: Entering an era","volume":"83","author":"Greenfield","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1212\/NXI.0000000000000405","article-title":"B-cell\u2013targeted therapies in relapsing forms of MS","volume":"4","author":"Dubey","year":"2017","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1004795","DOI":"10.3389\/fimmu.2023.1004795","article-title":"Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic","volume":"14","author":"Maillart","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e189442","DOI":"10.1172\/JCI189442","article-title":"Therapeutic B cell depletion identifies immunoregulatory networks","volume":"135","author":"Polonio","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"159","DOI":"10.35946\/arcr.v37.2.01","article-title":"Alcohol\u2019s Effect on Host Defense","volume":"37","author":"Szabo","year":"2015","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"185","DOI":"10.35946\/arcr.v37.2.04","article-title":"Impact of Alcohol Abuse on the Adaptive Immune System","volume":"37","author":"Pasala","year":"2015","journal-title":"Alcohol Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:30:35Z","timestamp":1773401435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biom16030427"],"URL":"https:\/\/doi.org\/10.3390\/biom16030427","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]}}}