{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:29:01Z","timestamp":1793158141037,"version":"4.5.0"},"reference-count":73,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS064571"],"award-info":[{"award-number":["NS064571"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32GM065841"],"award-info":[{"award-number":["T32GM065841"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS064571,T32GM065841"],"award-info":[{"award-number":["NS064571,T32GM065841"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:p>\n                    Multiple sclerosis is characterized by CNS infiltration of autoreactive immune cells that drive both acute inflammatory demyelination and chronic progressive axonal and neuronal injury. Expanding evidence implicates CD8\n                    <jats:sup>+<\/jats:sup>\n                    antineural T cells in the neurodegeneration that underlies irreversible clinical progression in multiple sclerosis, yet therapies specifically targeting this cell population are limited. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from patients with MS exhibit increased engagement of the pentose phosphate pathway. Pharmacologic inhibition of the pentose phosphate pathway reduced glycolysis, glucose uptake, NADPH production, ATP production, proliferation, and proinflammatory cytokine secretion in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells activated by ligation of CD3 and CD28. Pentose phosphate pathway inhibition also prevented CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated antigen-specific neuronal injury in vitro and in both an adoptive transfer\u2013based cuprizone model of demyelination and in mice with experimental autoimmune encephalomyelitis. Notably, transcriptional profiling of CNS-infiltrating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in patients with MS indicated increased pentose phosphate pathway engagement, suggesting that this pathway is involved in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated injury of axons and neurons in the demyelinated CNS. Inhibiting the pentose phosphate pathway disrupts CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell metabolic reprogramming and effector functions, suggesting that such inhibition may serve as a therapeutic strategy to prevent neurodegeneration in patients with progressive MS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184240","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T12:00:26Z","timestamp":1749556826000},"source":"Crossref","is-referenced-by-count":11,"title":["Pentose phosphate pathway inhibition metabolically reprograms CD8+ T cells and disrupts CNS autoimmunity"],"prefix":"10.1172","volume":"10","author":[{"given":"Ethan M.","family":"Grund","sequence":"first","affiliation":[{"name":"Mayo Graduate School,"},{"name":"Mayo Clinic Medical Scientist Training Program,"},{"name":"Translational Neuroimmunology Laboratory,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin 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