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生物节律对ILC3/Th17介导的肠道免疫应答的调控

Regulation of ILC3/Th17-Mediated Intestinal Immune Response by Circadian Rhythm

  • 摘要: 生物节律是一种被广泛认知的生物体随昼夜周期变化而呈现的生命活动周期性变化的现象。免疫系统的活跃状态也受到生物节律的调控。17型免疫应答是一种以转录因子类维生素A孤儿受体gamma t(RORγt)的表达以及白介素-17(IL-17)和白介素-22(IL-22)的分泌为特征的免疫反应类型,其过程主要由辅助性T细胞17(Th17)和三型天然淋巴细胞(ILC3)参与完成,与肠道免疫反应密切相关。近期研究发现,生物节律对Th17和ILC3介导的免疫应答有着精密调控,调控过程可通过各种节律调控分子完成,也可以在随着光照-黑暗周期变化而产生改变的其他外在因素,如饮食等的影响下完成。细胞因子的分泌则会伴随节律对Th17/ILC3的调控产生变化,进而对肠道细菌感染、自身免疫病等疾病发生和发展过程产生一定影响。研究免疫与节律的关系,可以更好地认知免疫系统的作用过程,为药物使用和疾病治疗提供重要理论依据。

     

    Abstract: The circadian rhythm is a widely-recognized phenomenon, according to which the life activities of organisms change periodically, synchronizing with the day and night cycles. The activities of the immune system are also regulated by the circadian rhythm. Group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) cells (ILC3/Th17) are the innate and adaptive subsets of immune cells mediating type 17 immune response, which is featured by the expression of transcription factor retinoid orphan receptor gamma t (RORγt) and the production of interleukin (IL)-17 and IL-22. The processes of type 17 immune response are completed mainly through the participation of ILC3/Th17 and are closely associated with the intestinal immune response. Recent studies have found that the immune response mediated by ILC3/Th17 is intricately regulated by the circadian rhythm through molecular mechanisms controlling the circadian rhythm, or through other external factors that change according to the light-darkness cycle, for example the food intake rhythm. The secretion of cytokines changes along with the regulatory effect of circadian rhythm on ILC3/Th17, which in turn impacts, to a certain degree, on the onset and development of intestinal inflammatory diseases, including bacterial infection and autoimmune diseases. The understanding of mechanisms regulating ILC3/Th17 responses by the circadian rhythm may promote better understanding of the course of action of the immune system and facilitate the development and discovery of potential targets for treatment of intestinal inflammatory diseases.

     

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