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

• Autores: Min Peng, Na Yin, Sagar Chhangawala
• Localización: Science, ISSN 0036-8075, Vol. 354, Nº 6311, 2016, págs. 482-484
• Idioma: inglés
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• Resumen

  • 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.