Control of macrophage metabolism and activation by mTOR and Akt signaling.
Control of macrophage metabolism and activation by mTOR and Akt signaling.
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DOI：
10.1016/j.smim.2015.08.001
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发表时间：
2015-08
影响因子：
7.8
通讯作者：
Horng T
中科院分区：
文献类型：
--
作者：
Covarrubias AJ;Aksoylar HI;Horng T
巨噬细胞是一种多效性细胞，根据其所在组织和组织状态的不同而具有多种功能。它们维持体内平衡，并协调对感染和代谢挑战等压力的反应。巨噬细胞获得多种环境依赖性活动的能力需要它们被激活（或极化）到不同的功能状态。虽然巨噬细胞的激活在信号转导和转录调控水平上得到了很好的理解，但其代谢基础却知之甚少。重要的是，新出现的研究表明，代谢变化在巨噬细胞激活和获取环境依赖性效应活性的控制中起着关键作用。驱动巨噬细胞激活的信号影响代谢途径，允许巨噬细胞激活和代谢的协调控制。我们将讨论这些激活信号的主要代谢调节因子和靶点mTOR和Akt如何控制巨噬细胞的代谢和激活。巨噬细胞活性失调导致许多疾病，包括感染性、炎症性、代谢性疾病和癌症，因此更好地了解巨噬细胞激活的代谢控制可以为开发新的治疗策略铺平道路。
Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies.