Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity Journal Article


Authors: Xu, K.; Yin, N.; Peng, M.; Stamatiades, E. G.; Shyu, A.; Li, P.; Zhang, X.; Do, M. H.; Wang, Z.; Capistrano, K. J.; Chou, C.; Levine, A. G.; Rudensky, A. Y.; Li, M. O.
Article Title: Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity
Abstract: Infection triggers expansion and effector differentiation of T cells specific for microbial antigens in association with metabolic reprograming. We found that the glycolytic enzyme lactate dehydrogenase A (LDHA) is induced in CD8+ T effector cells through phosphoinositide 3-kinase (PI3K) signaling. In turn, ablation of LDHA inhibits PI3K-dependent phosphorylation of Akt and its transcription factor target Foxo1, causing defective antimicrobial immunity. LDHA deficiency cripples cellular redox control and diminishes adenosine triphosphate (ATP) production in effector T cells, resulting in attenuated PI3K signaling. Thus, nutrient metabolism and growth factor signaling are highly integrated processes, with glycolytic ATP serving as a rheostat to gauge PI3K-Akt-Foxo1 signaling in the control of T cell immunity. Such a bioenergetic mechanism for the regulation of signaling may explain the Warburg effect. © 2021 American Association for the Advancement of Science. All rights reserved.
Keywords: signaling; enzyme activity; immunity; cell; reaction kinetics; gauge; cell component
Journal Title: Science
Volume: 371
Issue: 6527
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2021-01-22
Start Page: 405
End Page: 410
Language: English
DOI: 10.1126/science.abb2683
PUBMED: 33479154
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 March 2021 -- Source: Scopus
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MSK Authors
  1. Alexander Rudensky
    132 Rudensky
  2. Min Peng
    8 Peng
  3. Ming Li
    87 Li
  4. Na Yin
    6 Yin
  5. Ke   Xu
    8 Xu
  6. Andrew Gould Levine
    7 Levine
  7. Mytrang   Do
    10 Do
  8. Chun Chou
    7 Chou
  9. Xian Zhang
    5 Zhang
  10. Amy Shyu
    4 Shyu
  11. Peng Li
    4 Li
  12. Zhaoquan Wang
    1 Wang