Predoctoral student of the Cellular, Molecular, and Biomedical (CMB) Sciences Graduate Program at the University of Vermont, Burlington, VT, United States.
Department of Biomedical and Health Sciences, College of Nursing and Health Sciences, University of Vermont, Burlington, VT, United States.
Front Immunol. 2019 Jan 14;9:3145. doi: 10.3389/fimmu.2018.03145. eCollection 2018.
Dendritic cell (DC) activation is characterized by an acute increase in glucose metabolic flux that is required to fuel the high anabolic rates associated with DC activation. Inhibition of glycolysis significantly attenuates most aspects of DC immune effector function including antigen presentation, inflammatory cytokine production, and T cell stimulatory capacity. The cellular nutrient sensor mammalian/mechanistic Target of Rapamycin (mTOR) is an important upstream regulator of glycolytic metabolism and plays a central role in coordinating DC metabolic changes and immune responses. Because mTOR signaling can be activated by a variety of immunological stimuli, including signaling through the Toll-like Receptor (TLR) family of receptors, mTOR is involved in orchestrating many aspects of the DC metabolic response to microbial stimuli. It has become increasingly clear that mTOR's role in promoting or attenuating inflammatory processes in DCs is highly context-dependent and varies according to specific cellular subsets and the immunological conditions being studied. This review will address key aspects of the complex role of mTOR in regulating DC metabolism and effector function.
树突状细胞 (DC) 的激活表现为葡萄糖代谢通量的急剧增加，这是为了为 DC 激活相关的高合成代谢率提供燃料。糖酵解的抑制显著减弱了 DC 免疫效应功能的大多数方面，包括抗原呈递、炎症细胞因子的产生和 T 细胞刺激能力。细胞营养传感器哺乳动物/雷帕霉素靶蛋白 (mTOR) 是糖酵解代谢的重要上游调节剂，在协调 DC 代谢变化和免疫反应中发挥核心作用。由于 mTOR 信号可以被多种免疫刺激物激活，包括通过 Toll 样受体 (TLR) 家族受体的信号转导，mTOR 参与协调 DC 对微生物刺激的代谢反应的许多方面。越来越明显的是，mTOR 在促进或抑制 DC 中炎症过程中的作用高度依赖于上下文，并根据特定的细胞亚群和正在研究的免疫状况而有所不同。这篇综述将讨论 mTOR 在调节 DC 代谢和效应功能方面的复杂作用的关键方面。
