Chao Tung, Wang Haiping, Ho Ping-Chih
Department of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland.
Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland.
Front Immunol. 2017 Apr 24;8:473. doi: 10.3389/fimmu.2017.00473. eCollection 2017.
Immune cells protect us against infection and cancer cells, as well as functioning during healing processes to support tissue repairing and regeneration. These behaviors require that upon stimulation from immune activation the appropriate subsets of immune cells are generated. In addition to activation-induced signaling cascades, metabolic reprogramming (profound changes in metabolic pathways) also provides a novel form of regulation to control the formation of desirable immune responses. Immune cells encounter various nutrient compositions by circulating in bloodstream and infiltrating into peripheral tissues; therefore, proper engagement of metabolic pathways is critical to fulfill the metabolic demands of immune cells. Metabolic pathways are tightly regulated mainly mitochondrial dynamics and the activities of the tricarboxylic acid cycle and the electron transport chain. In this review, we will discuss how metabolic reprogramming influences activation, effector functions, and lineage polarization in T cells, with a particular focus on mitochondria-regulated metabolic checkpoints. Additionally, we will further explore how in various diseases deregulation and manipulation of mitochondrial regulation can occur and be exploited. Furthermore, we will discuss how this knowledge can facilitate the design of immunotherapies.
免疫细胞保护我们免受感染和癌细胞侵害，并且在愈合过程中发挥作用以支持组织修复和再生。这些行为要求在免疫激活的刺激下产生适当的免疫细胞亚群。除了激活诱导的信号级联反应外，代谢重编程（代谢途径的深刻变化）也提供了一种新的调节形式来控制所需免疫反应的形成。免疫细胞通过在血液中循环并浸润到外周组织中而遇到各种营养成分；因此，代谢途径的适当参与对于满足免疫细胞的代谢需求至关重要。代谢途径主要受线粒体动力学以及三羧酸循环和电子传递链的活动的严格调控。在这篇综述中，我们将讨论代谢重编程如何影响T细胞的激活、效应功能和谱系极化，特别关注线粒体调节的代谢检查点。此外，我们将进一步探讨在各种疾病中，线粒体调节的失调和操纵是如何发生以及被利用的。此外，我们将讨论这些知识如何促进免疫疗法的设计。
