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

doi:10.1126/science.abb2683

GSTDTAP > 气候变化

DOI	10.1126/science.abb2683
	Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity
	Ke Xu; Na Yin; Min Peng; Efstathios G. Stamatiades; Amy Shyu; Peng Li; Xian Zhang; Mytrang H. Do; Zhaoquan Wang; Kristelle J. Capistrano; Chun Chou; Andrew G. Levine; Alexander Y. Rudensky; Ming O. Li
	2021-01-22
发表期刊	Science
出版年	2021
英文摘要	Naïve T cells are metabolically reprogrammed when they differentiate into T effector (Teff) cells, transitioning from a reliance on mitochondrial oxidative phosphorylation to aerobic glycolysis. Xu et al. found that lactate dehydrogenase A (LDHA), a glycolytic enzyme that converts pyruvate to lactate, is a key player in this process. Teff cells that differentiate in mice infected with the bacterium Listeria monocytogenes turned on LDHA through phosphoinositide 3-kinase (PI3K) signaling. By promoting adenosine triphosphate (ATP) production, LDHA in turn facilitated PI3K-dependent inactivation of the transcription factor Foxo1 needed for effective Teff cell responses. Thus, glycolytic ATP acts like a rheostat that both gauges and regulates PI3K-dependent signaling. This type of positive feedback circuit may also provide a mechanistic explanation for the Warburg effect observed in cancer cells. Science , this issue p. [405][1] 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. [1]: /lookup/doi/10.1126/science.abb2683
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：167[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/312369
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Ke Xu,Na Yin,Min Peng,et al. Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity[J]. Science,2021.
APA	Ke Xu.,Na Yin.,Min Peng.,Efstathios G. Stamatiades.,Amy Shyu.,...&Ming O. Li.(2021).Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity.Science.
MLA	Ke Xu,et al."Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity".Science (2021).