Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism
Citations Over TimeTop 1% of 2016 papers
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-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.
Related Papers
- → Impairment of Aerobic Glycolysis by Inhibitors of Lactic Dehydrogenase Hinders the Growth of Human Hepatocellular Carcinoma Cell Lines(2010)60 cited
- → Oncogenic virus-induced aerobic glycolysis and tumorigenesis(2018)37 cited
- Role of the Intracellular pH in the Metabolic Switch between Oxidative Phosphorylation and Aerobic Glycolysis - Relevance to Cancer(2011)
- [Involvement of K+ in anerobic glycolysis of E. coli].(1982)
- → Aerobic Glycolysis and Its Role in Maintenance of High O2 Tensions in the Teleost Retina(1971)9 cited