Laboratorio de Cronobiología y Metabolismo, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Cell Infect Microbiol. 2020 Mar 13;10:96. doi: 10.3389/fcimb.2020.00096. eCollection 2020.
The circadian clock orchestrates daily rhythms in many physiological, behavioral and molecular processes, providing means to anticipate, and adapt to environmental changes. A specific role of the circadian clock is to coordinate functions of the immune system both at steady-state and in response to infectious threats. Hence, time-of-day dependent variables are found in the physiology of immune cells, host-parasite interactions, inflammatory processes, or adaptive immune responses. Interestingly, the molecular clock coordinates transcriptional-translational feedback loops which orchestrate daily oscillations in expression of many genes involved in cellular functions. This clock function is assisted by tightly controlled transitions in the chromatin fiber involving epigenetic mechanisms which determine how a when transcriptional oscillations occur. Immune cells are no exception, as they also present a functional clock dictating transcriptional rhythms. Hereby, the molecular clock and the chromatin regulators controlling rhythmicity represent a unique scaffold mediating the crosstalk between the circadian and the immune systems. Certain epigenetic regulators are shared between both systems and uncovering them and characterizing their dynamics can provide clues to design effective chronotherapeutic strategies for modulation of the immune system.
生物钟协调着许多生理、行为和分子过程的日常节律,为预测和适应环境变化提供了手段。生物钟的一个特定作用是协调免疫系统在稳态和应对感染威胁时的功能。因此,在免疫细胞的生理学、宿主-寄生虫相互作用、炎症过程或适应性免疫反应中都可以发现与时间相关的变量。有趣的是,分子钟协调着转录-翻译反馈环,这些反馈环协调着许多参与细胞功能的基因的日常振荡表达。这种时钟功能通过染色质纤维的严格控制的转变得到辅助,涉及决定转录振荡何时发生的表观遗传机制。免疫细胞也不例外,因为它们也呈现出一种功能性的时钟,决定着转录的节律。在这里,分子钟和控制节律的染色质调节剂代表了一个独特的支架,介导生物钟和免疫系统之间的串扰。某些表观遗传调节剂在这两个系统中是共享的,揭示它们并描述它们的动态可以为设计有效的时间治疗策略提供线索,以调节免疫系统。