Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism Journal Article
| Authors: | Peng, M.; Yin, N.; Chhangawala, S.; Xu, K.; Leslie, C. S.; Li, M. O. |
| Article Title: | Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism |
| 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-g 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. Copyright 2016 by the American Association for the Advancement of Science; all rights reserved. |
| Keywords: | mus |
| Journal Title: | Science |
| Volume: | 354 |
| Issue: | 6311 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2016-10-28 |
| Start Page: | 481 |
| End Page: | 484 |
| Language: | English |
| DOI: | 10.1126/science.aaf6284 |
| PROVIDER: | scopus |
| PUBMED: | 27708054 |
| PMCID: | PMC5539971 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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