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Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism.

ABSTRACT: Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T cells and has been implicated in augmenting effector T cell responses, including expression of the proinflammatory cytokine interferon-? (IFN-?), via 3' untranslated region (3'UTR)-mediated mechanisms. Here, we show that lactate dehydrogenase A (LDHA) is induced in activated T cells to support aerobic glycolysis but promotes IFN-? expression independently of its 3'UTR. Instead, LDHA maintains high concentrations of acetyl-coenzyme A to enhance histone acetylation and transcription of Ifng Ablation of LDHA in T cells protects mice from immunopathology triggered by excessive IFN-? expression or deficiency of regulatory T cells. These findings reveal an epigenetic mechanism by which aerobic glycolysis promotes effector T cell differentiation and suggest that LDHA may be targeted therapeutically in autoinflammatory diseases.

SUBMITTER: Peng M

PROVIDER: S-EPMC5539971 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism.

Peng Min M Yin Na N Chhangawala Sagar S Xu Ke K Leslie Christina S CS Li Ming O MO

Science (New York, N.Y.) 20160929 6311

Aerobic glycolysis (the Warburg effect) is a metabolic hallmark of activated T cells and has been implicated in augmenting effector T cell responses, including expression of the proinflammatory cytokine interferon-γ (IFN-γ), via 3' untranslated region (3'UTR)-mediated mechanisms. Here, we show that lactate dehydrogenase A (LDHA) is induced in activated T cells to support aerobic glycolysis but promotes IFN-γ expression independently of its 3'UTR. Instead, LDHA maintains high concentrations of ac ...[more]

PMID: 27708054

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Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism

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