Centre for Biogical Timing, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
Immunology. 2020 Dec;161(4):268-277. doi: 10.1111/imm.13167. Epub 2020 Jan 19.
The circadian clock provides organisms with the ability to track time of day, allowing them to predict and respond to cyclical changes in the external environment. In mammals this clock consists of multiple auto-regulatory feedback loops generated by a network of circadian clock proteins. This network provides the fundamental basis for rhythms in behaviour and physiology. This clockwork machinery exists in most cells, including those of the immune system. In recent years evidence has emerged highlighting the important role of molecular clocks in dictating the response of immune pathways. While initial work highlighted the effect of the clock in the 'first line of defence', the innate immune system, it has become increasingly apparent that it also plays a role in the more tailored, later-stage adaptive immune response. This review provides an overview of the role of the circadian cycle in the adaptive immune response. We interrogate the depth of knowledge on cell intrinsic clocks within adaptive immune cells and how these cells may be temporally directed by extrinsic rhythmic signals. We discuss the role of the circadian clock in diseases associated with adaptive immunity such as multiple sclerosis, asthma and parasitic infection. We also discuss the current knowledge on timing of vaccination, and the implications this may have on how we can harness and modulate temporal gating of the adaptive immune response in a clinical setting.
生物钟使生物体能够跟踪一天中的时间,使它们能够预测和应对外部环境的周期性变化。在哺乳动物中,这个时钟由多个由生物钟蛋白组成的自动调节反馈环组成。这个网络为行为和生理的节律提供了基本的基础。这个钟表机械装置存在于大多数细胞中,包括免疫系统的细胞。近年来,有证据表明分子钟在决定免疫途径的反应方面起着重要作用。虽然最初的工作强调了时钟在“第一道防线”即先天免疫系统中的作用,但它在更具针对性的后期适应性免疫反应中也起着重要作用。这篇综述概述了生物钟在适应性免疫反应中的作用。我们探讨了适应性免疫细胞中细胞内在时钟的深度知识,以及这些细胞如何受到外在节律信号的时间指导。我们讨论了生物钟在与适应性免疫相关的疾病(如多发性硬化症、哮喘和寄生虫感染)中的作用。我们还讨论了关于疫苗接种时间的现有知识,以及这可能对我们如何在临床环境中利用和调节适应性免疫反应的时间门控产生的影响。