{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:01:19Z","timestamp":1780646479568,"version":"3.54.1"},"reference-count":33,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100020463","name":"Valhalla Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020463","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Mucosal-associated invariant T (MAIT) cells recognize microbial vitamin B2 and B9 metabolites via MR1 and have been implicated in multiple sclerosis (MS). How patient-specific gut microbiota shape human MAIT-cell pathogenicity at the clonal level remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods:<\/jats:title>\n                    <jats:p>We generated 62 MAIT-cell clones from relapsing\u2013remitting multiple sclerosis (RRMS) patients and 50 from healthy controls (HCs). Clones were stimulated with riboflavin- or folate-pathway metabolites, paraformaldehyde-fixed patient-matched gut bacterial isolates, or interleukin (IL)-12\/IL-18. Activation markers, cytokine secretion, cytotoxicity, and competitive MR1\u2013ligand inhibition were assessed. Intestinal permeability was evaluated using I-FABP, LBP, GLP-2, and fecal \u03b1-1-antitrypsin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>MS-derived MAIT clones showed markedly enhanced activation, increased interferon-gamma (IFN-\u03b3), IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, and greater cytotoxicity compared with HCs when stimulated with riboflavin-producing taxa isolated from the same patients. Importantly, several responses diverged from predictions based on murine models and genomic inference, including mixed cytokine profiles and graded competitive inhibition by folate-derived ligands. These findings highlight species-specific differences in MR1 ligand handling and MAIT-cell activation. Activation required uptake of intact bacteria and acid-dependent MR1 loading. MS patients exhibited significant intestinal barrier dysfunction, linking dysbiosis to systemic MAIT-cell hyperactivation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>At clonal resolution, this study demonstrates that patient-specific microbial metabolism, MR1\u2013ligand competition, and epithelial barrier disruption cooperate to amplify MAIT-cell pathogenicity in MS, revealing human-specific mechanisms not predicted by animal models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261447695","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:50:36Z","timestamp":1780336236000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-derived metabolites from vitamin B2 and B9 pathways modulate MAIT cells from multiple sclerosis patients"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-9889","authenticated-orcid":false,"given":"Jorge","family":"Correale","sequence":"first","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina; Institute of Biological Biochemistry and Biophysics (IQUIFIB), University of Buenos Aires, Buenos Aires, Argentina; Center for Research on Neuroimmunological Diseases (CIEN), Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-8375","authenticated-orcid":false,"given":"Mariano","family":"Marrodan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4352-5002","authenticated-orcid":false,"given":"Maria A","family":"Piedrabuena","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Soman","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio F","family":"Farez","sequence":"additional","affiliation":[{"name":"Center for Research on Neuroimmunological Diseases (CIEN), Fleni, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0067-194X","authenticated-orcid":false,"given":"Sergio E","family":"Baranzini","sequence":"additional","affiliation":[{"name":"Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30481-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0444-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26250"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.1.1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01433"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11605"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13160"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02690"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.81"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00503"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.039"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445313"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.585134"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814558116"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.11.021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344160"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.890298"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53657-9"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22366"},{"issue":"19","key":"e_1_3_3_23_2","article-title":"Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course","volume":"185","author":"The iMSMS Consortium","year":"2022","unstructured":"The iMSMS Consortium. Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course. 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