Evidence supporting a circadian control of natural killer cell function
Evidence supporting a circadian control of natural killer cell function
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DOI：
10.1016/j.bbi.2005.10.002
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发表时间：
2006-09-01
影响因子：
15.1
通讯作者：
Sarkar, Dipak K.
中科院分区：
文献类型：
--
作者：
Arjona, Alvaro;Sarkar, Dipak K.
自然杀伤(NK)细胞参与对抗感染和癌症的免疫反应。一组新的流行病学数据支持昼夜节律平衡可能构成癌症发展的一个因素风险。在昼夜节律控制下，生理节律在没有光夹带的情况下持续存在，并最终依赖于分子时钟。我们之前已经证明，NK细胞的杀伤活性遵循每日的节律，从光诱导的大鼠身上获得的NK细胞呈现时钟基因、细胞溶解因子和细胞因子的24小时振荡。为了研究这些振荡是否受到真正的昼夜节律控制，我们评估了时钟基因(PER1、PER2、CLOCK和BMal1)、时钟控制基因(DBP)、细胞溶解因子(颗粒酶B和PERFORE)以及细胞因子(干扰素-伽马和肿瘤坏死因子-α)在持续黑暗(DD)中丰富的大鼠NK细胞中的日常表达。此外，我们还研究了RNA干扰(RNAi)对NK细胞时钟的干扰是否会影响细胞溶解因子和细胞因子的表达。DD大鼠NK细胞中时钟基因、细胞溶解因子和细胞因子的表达水平存在持续的24小时振荡。此外，RNAi介导的PER2基因敲除导致大鼠来源的NK细胞系RNK16中颗粒酶B和穿孔素水平显著降低。综上所述，这些结果提供了支持NK细胞功能受昼夜节律调节的证据。(C)2005 Elsevier Inc.保留所有权利。
Natural killer (NK) cells participate in the immune response against infection and cancer. An emerging body of epidemiological data supports that circadian homeostasis may constitute a factor risk for cancer development. Physiological rhythms under circadian control persist in the absence of light entrainment and ultimately rely on a molecular clock. We have previously shown that NK cell cytolytic activity follows a daily rhythm and that NK cells enriched from light-entrained rats present 24-h oscillations of clock genes, cytolytic factors, and cytokines. To investigate whether these oscillations are under a genuine circadian control, we assessed the daily expression of clock genes (Per1, Per2, Clock, and Bmal1), a clock-controlled gene (Dbp), cytolytic factors (granzyme B and perform), and cytokines (IFN-gamma and TNF-alpha) in NK cells enriched from rats maintained in constant darkness (DD). In addition, we investigated whether the disruption of the NK cell clock by RNA interference (RNAi) affects the expression of cytolytic factors and cytokines. Persistent 24-h oscillations were found in the expression levels of clock genes, cytolytic factors, and cytokines in NK cells enriched from DD rats. In addition, RNAi-mediated Per2 knockdown caused a significant decrease of granzyme B and perforin levels in the rat derived NK cell line RNK16. Taken together, these results provide evidence supporting that NK cell function is under circadian regulation. (c) 2005 Elsevier Inc. All rights reserved.