Labrecque Nathalie, Cermakian Nicolas
Maisonneuve-Rosemont Hospital Research Center, Montréal, Quebec, Canada, and Departments of Medicine, and Microbiology, Infectiology and Immunology, University of Montreal, Montréal, Quebec, Canada.
Douglas Mental Health University Institute, Departments of Psychiatry, Microbiology & Immunology, Neurology & Neurosurgery, Physiology, McGill University, Montréal, QC, Canada
J Biol Rhythms. 2015 Aug;30(4):277-90. doi: 10.1177/0748730415577723. Epub 2015 Apr 20.
The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address.
免疫系统是一套复杂的生理机制，其总体目标是保护机体抵御非自身物质，如病原体（细菌、病毒、寄生虫）以及癌细胞。昼夜节律是几乎在所有生理过程中都存在的内源性24小时变化。这些昼夜节律由生物钟产生，生物钟存在于大多数细胞类型中，包括免疫系统的细胞。本综述概述了免疫系统中的生物钟以及免疫细胞功能的昼夜调节。大多数免疫细胞表达昼夜节律时钟基因，并呈现出大量以24小时节律表达的基因。这对细胞功能有深远影响，包括细胞因子、趋化因子和溶细胞因子合成与释放的每日节律、通过模式识别受体发生的反应的每日门控、吞噬作用、迁移至炎症或感染组织、溶细胞活性以及对抗原的增殖反应等细胞功能的昼夜节律。因此，昼夜节律的改变（例如，小鼠中的时钟基因突变或类似于轮班工作的环境干扰）会导致免疫反应紊乱。我们讨论了这些数据对人类健康的影响以及未来研究应致力于解决的领域。
