ArticleScience advances2026
Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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-mediated 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-mediated 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.
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