{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:58:39Z","timestamp":1790787519911,"version":"4.1.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"813","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,8,27]]},"abstract":"<jats:p>\n            Follicular regulatory T cells (T\n            <jats:sub>fr<\/jats:sub>\n            cells) constitute a subset of regulatory T cells pivotal to the immune response in germinal centers (GCs) that inhibit autoantibody production. Their role, however, remains ill-defined in autoimmune diseases like multiple sclerosis (MS) and its murine model, experimental autoimmune encephalomyelitis (EAE), which are neuroinflammatory diseases driven by T and B cells. Here, we quantified peripheral blood immune subpopulations in two cohorts of patients with MS and found higher circulating T\n            <jats:sub>fr<\/jats:sub>\n            cell frequencies in patients in relapse compared with patients in remission. To examine the functional role of T\n            <jats:sub>fr<\/jats:sub>\n            cells in autoimmune neuroinflammation, we used EAE mouse models and showed that Foxp3\n            <jats:sup>cre\/cre<\/jats:sup>\n            Bcl6\n            <jats:sup>fl\/fl<\/jats:sup>\n            T\n            <jats:sub>fr<\/jats:sub>\n            cell\u2013deficient mice developed milder EAE than wild-type (WT) mice. Flow cytometry analysis demonstrated that the reduction of encephalomyelitis in T\n            <jats:sub>fr<\/jats:sub>\n            cell\u2013deficient mice was associated with fewer B cells infiltrating the central nervous system. Coculture experiments showed that B cells isolated from brains of WT mice at the peak of the disease fostered pro-inflammatory cytokine production by myelin oligodendrocyte glycoprotein\u2013specific T cells. We furthermore showed that sphingosine-1-phosphate receptor 2 (S1PR2) expression in GC B cells was up-regulated in T\n            <jats:sub>fr<\/jats:sub>\n            cell\u2013deficient mice. Treatment with an S1PR2 receptor antagonist abrogated the improved EAE clinical scores in T\n            <jats:sub>fr<\/jats:sub>\n            cell\u2013deficient mice, and this loss of protection was associated with increased B cell infiltration into the brain and increased pro-inflammatory cytokine production by encephalitogenic T cells. These findings demonstrate that T\n            <jats:sub>fr<\/jats:sub>\n            cells contribute to autoimmune encephalomyelitis and suggest that their blood frequency reflects MS activity.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ady1268","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:58:41Z","timestamp":1756317521000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Follicular regulatory T cells promote experimental autoimmune encephalomyelitis by supporting B cell egress from germinal centers"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-0759","authenticated-orcid":true,"given":"Fanny","family":"Martinez","sequence":"first","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coline","family":"Cotineau","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-1801","authenticated-orcid":true,"given":"Julien","family":"Novarino","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-1710","authenticated-orcid":true,"given":"Cyrielle","family":"Bories","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2604-5927","authenticated-orcid":true,"given":"Louis","family":"Culie","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7119-5263","authenticated-orcid":true,"given":"Stephane","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"UMR_ S 1236, INSERM, Univ Rennes, EFS Bretagne, F-35000 Rennes, France."},{"name":"SITI, CHU de Rennes, EFS Bretagne, F-35000 Rennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine","family":"P\u00e9rals","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7992-8423","authenticated-orcid":true,"given":"Simon","family":"Lachambre","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2779-6584","authenticated-orcid":true,"given":"Val\u00e9rie","family":"Duplan-Eche","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2368-9165","authenticated-orcid":true,"given":"Florence","family":"Bucciarelli","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Pignolet","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-5475","authenticated-orcid":true,"given":"Roland S.","family":"Liblau","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8119-7794","authenticated-orcid":true,"given":"Laure","family":"Michel","sequence":"additional","affiliation":[{"name":"UMR_ S 1236, INSERM, Univ Rennes, EFS Bretagne, F-35000 Rennes, France."},{"name":"SITI, CHU de Rennes, EFS Bretagne, F-35000 Rennes, France."},{"name":"Neurology Department, Rennes University Hospital, Rennes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4590-230X","authenticated-orcid":true,"given":"Meryem","family":"Aloulou","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3574-5614","authenticated-orcid":true,"given":"Nicolas","family":"Fazilleau","sequence":"additional","affiliation":[{"name":"Univ Toulouse, INSERM, CNRS, Infinity, Toulouse, 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