The circadian gene mPer2 regulates the daily rhythm of IFN-γ
The circadian gene mPer2 regulates the daily rhythm of IFN-γ
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DOI：
10.1089/jir.2006.26.645
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发表时间：
2006-09-01
影响因子：
2.3
通讯作者：
Sarkar, Dipak K.
中科院分区：
文献类型：
--
作者：
Arjona, Alvaro;Sarkar, Dipak K.
昼夜节律和日常节奏调节生理和行为的许多方面。虽然越来越多的研究表明，昼夜节律的破坏可能使生物体更容易感染和癌症，昼夜节律系统和免疫系统之间的分子联系在很大程度上是未知的。在这里，我们报告说，小鼠携带Per 2基因，分子生物钟的关键组成部分的功能丧失突变，缺乏生理的每日节律的干扰素-γ（IFN-γ）mRNA和蛋白质表达在脾脏。这些观察结果与典型时钟基因表达的显著改变有关。此外，Per 2突变小鼠未能显示IFN-γ血清水平的每日节律，其显著低于在早期光照期间在野生型小鼠中测定的水平。这些发现为IFN-γ的直接昼夜调节提供了新的证据，IFN-γ是调节免疫应答的关键细胞因子。
Circadian and daily rhythms regulate many aspects of physiology and behavior. Although a growing number of studies suggest that circadian disruptions may render organisms more susceptible to infection and cancer, the molecular links between the circadian system and the immune system are largely unknown. Here we report that mice carrying a loss-of-function mutation in the Per2 gene, a key component of the molecular circadian clock, lacked the physiologic daily rhythm of interferon-gamma ( IFN-gamma) mRNA and protein expression in the spleen. These observations were associated with a significant alteration in the expression of canonical clock genes. In addition, Per2 mutant mice failed to show a daily rhythm in IFN-gamma serum levels, which were significantly lower than those determined in wild-type mice during the early light period. These findings provide novel evidence for a direct circadian regulation of IFN-gamma, a critical cytokine modulating the immune response.