{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T12:28:45Z","timestamp":1777984125478,"version":"3.51.4"},"posted":{"date-parts":[[2025,6,11]]},"group-title":"Immunology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Amino acids play critical roles in the activation and function of lymphocytes. Here we show that the non-essential amino acid, asparagine, is essential for optimal activation and proliferation of CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells. We demonstrate that asparagine depletion at different time points after CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell activation reduces mitochondrial membrane potential and function. Furthermore, asparagine depletion at specific time points during CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell differentiation reduces cytokine production in multiple CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell subsets. In an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE), myelin oligodendrocyte-specific pathogenic T helper 17 cells differentiated under Asn-deficient conditions exhibited reduced encephalitogenic potential and attenuated EAE severity. In a model of EAE induced by active immunization, therapeutic depletion of extracellular Asn significantly reduced disease severity. These results identify asparagine as a key metabolic regulator of the pathogenicity of autoreactive CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells and suggest that targeting asparagine metabolism may be a novel therapeutic strategy for autoimmunity.\n                <\/jats:p>","DOI":"10.1101\/2025.06.09.658561","type":"posted-content","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T21:20:16Z","timestamp":1749676816000},"source":"Crossref","is-referenced-by-count":0,"title":["Depletion of extracellular asparagine impairs self-reactive T cells and ameliorates autoimmunity in a murine model of multiple sclerosis"],"prefix":"10.64898","author":[{"given":"Peter","family":"Georgiev","sequence":"first","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA"},{"name":"Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA"},{"name":"Gene Lay Institute of Immunology and Inflammation of Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-7934","authenticated-orcid":false,"given":"Sheila","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA"},{"name":"Gene Lay Institute of Immunology and Inflammation of Brigham and Women\u2019s Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiran","family":"Kurmi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, 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