{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:42:30Z","timestamp":1792024950393,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_214931"],"award-info":[{"award-number":["310030_214931"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P500PM_222181"],"award-info":[{"award-number":["P500PM_222181"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hepatocyte growth factor (HGF) binds exclusively\u00a0the c\u2010Met surface receptor, and the HGF\/c\u2010Met axis regulates T cell function in autoimmune diseases. We analyzed c\u2010Met expression on human CD4 T cells in the blood and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) versus non\u2010inflammatory neurological disease (NIND), to better understand the role of CD4 T cells in MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We recruited 34 untreated MS patients (age 28\u201344\u2009years) and 13 NIND (age 34\u201351\u2009years) who underwent paired blood and CSF sampling at the time of diagnosis work\u2010up. Phenotypic and functional CD4 T cells characterization was determined by flow cytometry and bulk RNA sequencing. Adhesion and transmigration capacities were studied to further characterize the function of c\u2010Met\n                      <jats:sup>+<\/jats:sup>\n                      CD4 T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      c\u2010Met\n                      <jats:sup>+<\/jats:sup>\n                      memory CD4 T cells were detected at higher levels in both blood (median of 1.98%) and CSF (5.88%) in MS compared to NIND (0.37% and 0.68%, respectively) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Ex vivo c\u2010Met\n                      <jats:sup>+<\/jats:sup>\n                      CD4 T cells exhibited higher levels of GM\u2010CSF, interleukin (IL)\u201017, interferon (IFN)\u2010, and double positive IL\u201017\n                      <jats:sup>+<\/jats:sup>\n                      IFN\u2010\n                      <jats:sup>+<\/jats:sup>\n                      expression, compared with c\u2010Met\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD4 T cells. c\u2010Met\n                      <jats:sup>+<\/jats:sup>\n                      CD4 T cells expressed increased levels of integrins\u2014Itg\u03b14\u03b21 (VLA\u20104) and Itg\u03b1L\u03b22 (LFA\u20101)\u2014compared with c\u2010Met\n                      <jats:sup>\u2212<\/jats:sup>\n                      CD4 T cells. Anti\u2010Itg\u03b14 (natalizumab) and anti\u2010Itg\u03b1L\u03b22 (odulimomab) inhibited CD4 T cell transmigration with predominant inhibition of CD4 T cells expressing c\u2010Met.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These results emphasize c\u2010Met as an immune marker of highly pro\u2010inflammatory and migratory CD4 T lymphocytes in both the periphery and central nervous system of MS patients. ANN NEUROL 2026;99:261\u2013273<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78035","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:35:44Z","timestamp":1758890144000},"page":"261-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pro\u2010Inflammatory\n                    <scp>c<\/scp>\n                    \u2010Met\n                    <sup>+<\/sup>\n                    <scp>CD4<\/scp>\n                    T Cells in Multiple Sclerosis"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-1981","authenticated-orcid":false,"given":"Gautier","family":"Breville","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, Division of Neurology University Hospital of Geneva  Geneva Switzerland"},{"name":"Department of Pathology and Immunology Faculty of Medicine, University of Geneva  Geneva 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