Other
14 Authors
- Peng M,
- Zhang X,
- Do MH,
- Chou C,
- Yin N,
- Li P,
- Stamatiades EG,
- Capistrano KJ,
- Wang Z,
- Xu K,
- Shyu A,
- Levine AG,
- Rudensky AY,
- Li MO
| First Author | Xu K | Year | 2021 |
| Journal | Science | Volume | 371 |
| Issue | 6527 | Pages | 405-410 |
| PubMed ID | 33479154 | Mgi Jnum | J:301027 |
| Mgi Id | MGI:6501797 | Doi | 10.1126/science.abb2683 |
| Citation | Xu K, et al. (2021) Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity. Science 371(6527):405-410 |
| abstractText | 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. |
