美国纪念斯隆·凯特琳癌症中心Ming O. Li研究组取得最新进展。糖酵解促进磷酸肌醇3-激酶（PI3K）信号传导，以增强T细胞免疫力。相关论文于2021年1月22日发表于《科学》杂志。

他们发现糖酵解乳酸脱氢酶A（LDHA）通过PI3K信号传导在CD8 + T效应细胞中被诱导。相反，LDHA的敲除抑制了PI3K依赖的Akt磷酸化及其转录因子靶向Foxo1，导致抗微生物免疫力下降。LDHA缺乏会削弱细胞的氧化还原控制并减少效应T细胞中三磷酸腺苷（ATP）的产生，从而导致PI3K信号减弱。

因此，营养物质代谢和生长因子信号传导是高度整合的过程，糖酵解ATP用作变阻剂，以测量T3细胞免疫控制中的PI3K-Akt-Foxo1信号传导。这种调节信号传导的生物能机制可以解释沃伯格效应。

研究人员表示，感染会触发与微生物重编程相关的微生物抗原特异性T细胞的扩增和效应分化。

附：英文原文

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

Author: 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

Issue&Volume: 2021/01/22

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.

DOI: 10.1126/science.abb2683

Source: https://science.sciencemag.org/content/371/6527/405