Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; email:
National Key Laboratory of Medical Immunology, Institute of Immunology, Navy Military Medical University, Shanghai 200433, China.
Annu Rev Immunol. 2021 Apr 26;39:279-311. doi: 10.1146/annurev-immunol-093019-123619. Epub 2021 Feb 5.
The innate immune response is a rapid response to pathogens or danger signals. It is precisely activated not only to efficiently eliminate pathogens but also to avoid excessive inflammation and tissue damage. -Regulatory element-associated chromatin architecture shaped by epigenetic factors, which we define as the epiregulome, endows innate immune cells with specialized phenotypes and unique functions by establishing cell-specific gene expression patterns, and it also contributes to resolution of the inflammatory response. In this review, we focus on two aspects: () how niche signals during lineage commitment or following infection and pathogenic stress program epiregulomes by regulating gene expression levels, enzymatic activities, or gene-specific targeting of chromatin modifiers and () how the programed epiregulomes in turn mediate regulation of gene-specific expression, which contributes to controlling the development of innate cells, or the response to infection and inflammation, in a timely manner. We also discuss the effects of innate immunometabolic rewiring on epiregulomes and speculate on several future challenges to be encountered during the exploration of the master regulators of epiregulomes in innate immunity and inflammation.
先天免疫反应是对病原体或危险信号的快速反应。它不仅能有效地消除病原体,而且能避免过度的炎症和组织损伤。——由表观遗传因素塑造的与调节元件相关的染色质结构,我们将其定义为表观调控组,通过建立细胞特异性基因表达模式,赋予先天免疫细胞特化的表型和独特的功能,也有助于炎症反应的解决。在这篇综述中,我们关注两个方面:() 在谱系确定或感染和致病应激后,龛位信号如何通过调节基因表达水平、酶活性或染色质修饰物的基因特异性靶向来调控表观调控组;() 程序化的表观调控组反过来如何介导基因特异性表达的调控,从而有助于控制先天细胞的发育,或及时对感染和炎症做出反应。我们还讨论了先天免疫代谢重编程对表观调控组的影响,并推测在探索先天免疫和炎症中表观调控组的主调控因子时将遇到的几个未来挑战。