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Pyruvate Kinase Muscle (PKM)-2 promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion

ABSTRACT: Glycolysis is an essential metabolic pathway for rapidly expanding T cells, but role of Pyruvate Kinase Muscle (PKM) 1 and 2 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 2 in regulating CD4 T cell survival during homeostasis and expansion. Expanding PKM2-deficient CD4 T cells increased PKM1 expression with associated mitochondrial ROS-mediated cell death. Examination of T cell compartments revealed PKM2-deficient CD4 T cells were unaltered in the thymus but were significantly reduced in peripheral tissues as mice aged. The failure of PKM1 to protect CD4 T cells in the absence of PKM2 resulted in protection from T cell mediated colitis as pathogenic cell numbers were significantly reduced resulting in less severe disease compared to control cells. This study shows PKM2 is critical for CD4 T cell survival during expansion and homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE310321 | GEO | 2025/11/24

REPOSITORIES: GEO

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PKM splice-switching ASOs induce upregulation of dual-specificity phosphatases and dephosphorylation of ERK1/2 in hepatocellular carcinoma

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Expression data from PKM1 or PKM2 expressing mouse embryonic fibroblasts.

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