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

作者：Min Peng, Na Yin, Sagar Chhangawala, Ke Xu, Christina S. Leslie, Ming O. Li · 发表于：Science · 年份：2016 · DOI：10.1126/science.aaf6284 · 被引用次数：789 · 研究领域：Immune Cell Function and Interaction、Immune cells in cancer、Cancer, Hypoxia, and Metabolism

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.