Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism
2016; American Association for the Advancement of Science; Volume: 354; Issue: 6311 Linguagem: Inglês
10.1126/science.aaf6284
ISSN1095-9203
AutoresMin Peng, Na Yin, Sagar Chhangawala, Ke Xu, Christina Leslie, Ming O. Li,
Tópico(s)Cancer, Hypoxia, and Metabolism
ResumoAerobic 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.
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