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

M Peng, N Yin, S Chhangawala, K Xu, CS Leslie… - Science, 2016 - science.org
M Peng, N Yin, S Chhangawala, K Xu, CS Leslie, MO Li
Science, 2016science.org
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 acetyl–coenzyme A to …
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 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-γ 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.
AAAS