Phan Anthony T, Goldrath Ananda W, Glass Christopher K
Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Immunity. 2017 May 16;46(5):714-729. doi: 10.1016/j.immuni.2017.04.016.
Recognition of pathogens by innate and adaptive immune cells instructs rapid alterations of cellular processes to promote effective resolution of infection. To accommodate increased bioenergetic and biosynthetic demands, metabolic pathways are harnessed to maximize proliferation and effector molecule production. In parallel, activation initiates context-specific gene-expression programs that drive effector functions and cell fates that correlate with changes in epigenetic landscapes. Many chromatin- and DNA-modifying enzymes make use of substrates and cofactors that are intermediates of metabolic pathways, providing potential cross talk between metabolism and epigenetic regulation of gene expression. In this review, we discuss recent studies of T cells and macrophages supporting a role for metabolic activity in integrating environmental signals with activation-induced gene-expression programs through modulation of the epigenome and speculate as to how this may influence context-specific macrophage and T cell responses to infection.
天然免疫细胞和适应性免疫细胞对病原体的识别会促使细胞过程迅速改变，以促进感染的有效消除。为了满足增加的生物能量和生物合成需求，代谢途径被利用来最大化增殖和效应分子的产生。与此同时，激活启动了特定背景的基因表达程序，这些程序驱动效应功能和细胞命运，而这些与表观遗传景观的变化相关。许多染色质和DNA修饰酶利用代谢途径的中间产物作为底物和辅助因子，这为代谢与基因表达的表观遗传调控之间提供了潜在的相互作用。在这篇综述中，我们讨论了关于T细胞和巨噬细胞的最新研究，这些研究支持代谢活动在通过表观基因组的调节将环境信号与激活诱导的基因表达程序整合方面所起的作用，并推测这可能如何影响巨噬细胞和T细胞对感染的特定背景反应。
