The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity.

The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity.
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DOI:
10.1016/j.immuni.2011.12.017
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发表时间:
2012-02-24
期刊:
影响因子:
32.4
通讯作者:
Fikrig E
Fikrig E
中科院分区:
医学1区
文献类型:
--
作者:
Silver AC;Arjona A;Walker WE;Fikrig E

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昼夜节律是指以大约24小时的周期振荡的生物过程。这些节律由分子钟维持,并提供了一个时间矩阵,以确保稳态过程与环境挑战的周期性相协调。我们证明了昼夜分子钟控制Toll样受体9(TLR9)的表达和功能。在使用TLR9配体作为佐剂的疫苗接种模型中,在增强的TLR9应答性时免疫的小鼠在数周后呈现出改善的适应性免疫应答。在TLR9依赖性脓毒症小鼠模型中,我们发现疾病严重程度依赖于脓毒症诱导的时间,与TLR9表达和功能的每日变化一致。这些发现揭示了昼夜节律和先天免疫系统之间的直接分子联系,对免疫预防和免疫治疗具有重要意义。
Circadian rhythms refer to biologic processes that oscillate with a period of approximately 24 hours. These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of homeostatic processes with the periodicity of environmental challenges. We demonstrate the circadian molecular clock controls the expression and function of toll like receptor 9 (TLR9). In a vaccination model using TLR9 ligand as adjuvant, mice immunized at the time of enhanced TLR9 responsiveness presented weeks later with an improved adaptive immune response. In a TLR9-dependent mouse model of sepsis, we found that disease severity was dependent on the timing of sepsis induction, coinciding with the daily changes in TLR9 expression and function. These findings unveil a direct molecular link between the circadian and innate immune systems with important implications for immunoprophylaxis and immunotherapy.
DOI: 10.3109/08830189809043012
发表时间: 1998-01-01
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