| First Author | Peng M | Year | 2016 |
| Journal | Science | Volume | 354 |
| Issue | 6311 | Pages | 481-484 |
| PubMed ID | 27708054 | Mgi Jnum | J:314934 |
| Mgi Id | MGI:6771769 | Doi | 10.1126/science.aaf6284 |
| Citation | Peng M, et al. (2016) Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science 354(6311):481-484 |
| abstractText | 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-gamma (IFN-gamma), 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-gamma 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-gamma 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. |
