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Adv."],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:p>Glycolysis is an essential metabolic pathway for rapidly expanding T cells, but the role of pyruvate kinase muscle 1 (PKM1) and PKM2 in regulating this process is underappreciated. Here, using a pharmacological activator and targeted deletion of PKM2 in T cells, we delineated distinct functions of PKM1 and PKM2 in regulating CD4 T cell survival during homeostasis and expansion. Expanding PKM2-deficient CD4 T cells increased PKM1 expression with associated mitochondrial reactive oxygen species\u2013mediated cell death. Examination of T cell compartments revealed that PKM2-deficient CD4 T cells were unaltered in the thymus but were significantly reduced in peripheral tissues as mice aged. The inability of PKM1 to protect CD4 T cells in the absence of PKM2 led to less severe T cell\u2013mediated colitis as PKM2-deficient pathogenic cells were significantly reduced compared with control cells. This study shows that PKM2 is critical for CD4 T cell survival during expansion and homeostasis.<\/jats:p>","DOI":"10.1126\/sciadv.aec5092","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T18:58:16Z","timestamp":1769799496000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7442-1807","authenticated-orcid":true,"given":"Jeff J.","family":"Subleski","sequence":"first","affiliation":[{"name":"Cancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-5324","authenticated-orcid":true,"given":"Erika 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