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
Altmetric Score
MSK Authors
  1. Min Peng
    5 Peng
  2. Christina Leslie
    111 Leslie
  3. Ming Li
    67 Li
  4. Na Yin
    4 Yin
  5. Ke   Xu
    4 Xu