Role of sympathetic nervous system in the entrainment of circadian natural-killer cell function.
Role of sympathetic nervous system in the entrainment of circadian natural-killer cell function.
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DOI：
10.1016/j.bbi.2010.08.007
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发表时间：
2011-01
影响因子：
15.1
通讯作者：
Sarkar, Dipak K.
中科院分区：
文献类型：
--
作者：
Logan, Ryan W.;Arjona, Alvaro;Sarkar, Dipak K.
关键词：
我们实验室先前的研究已经证明了来自大鼠脾脏的富集NK细胞中细胞因子和细胞溶解因子的强大昼夜变化，强烈表明这些功能可能受到昼夜调节。SCN通过体液和神经输入将时间信息介导到外周组织。特别地，去甲肾上腺素能（NE）交感神经系统（SNS）终末支配脾组织，在中枢和外周系统之间传递信息。然而，这些免疫因子是否受到通过神经NE神经支配传递到脾脏的时间信息仍然未知。事实上，我们能够表征NE含量在脾脏中的昼夜节律，支持SNS作为脾细胞定时信息的传送器的作用。通过乙啶处理化学产生局部脾交感神经切除术，脾NE节律被消除或移动，如ZT 7处预期峰的钝化所示。因此，NK细胞和脾细胞中细胞因子TNF-α和细胞溶解因子颗粒酶B和穿孔素的日变化发生了改变。脾细胞中IFN-γ的mRNA表达只有时间依赖性改变，而NK细胞中的蛋白水平没有改变，这表明非神经夹带信号可能是调节特异性免疫因子所必需的。此外，这些组织中的时钟基因和蛋白质Bmal 1和Per 2的节律也显示出显著改变的每日变化。总的来说，这些结果表明，有节奏的NE输入到脾脏作为一个夹带线索，以调节NK细胞和其他脾细胞的分子时钟可能发挥作用，在调节这些细胞的细胞因子和细胞溶解功能。
Previous research in our laboratory has demonstrated robust circadian variations of cytokines and cytolytic factors in enriched NK cells from rat spleen, strongly suggesting these functions may be subject to circadian regulation. The SCN mediates timing information to peripheral tissues by both humoral and neural inputs. In particular, noradrenergic (NE) sympathetic nervous system (SNS) terminals innervate the spleen tissue communicating information between central and peripheral systems. However, whether these immune factors are subject to timing information conveyed through neural NE innervation to the spleen remained unknown. Indeed, we were able to characterize a circadian rhythm of NE content in the spleen, supporting the role of the SNS as a conveyor of timing information to splenocytes. By chemically producing a local splenic sympathectomy through guanethidine treatment, the splenic NE rhythm was abolished or shifted as indicated by a blunting of the expected peak at ZT7. Consequently, the daily variations of cytokine, TNF-α, and cytolytic factors, granzyme-B and perforin, in NK cells and splenocytes were altered. Only time-dependent mRNA expression of IFN-γ was altered in splenocytes, but not protein levels in NK cells, suggesting non-neural entrainment cues may be necessary to regulate specific immune factors. In addition, the rhythms of clock genes and proteins, Bmal1 and Per2, in these tissues also displayed significantly altered daily variations. Collectively, these results demonstrate rhythmic NE input to the spleen acts as an entrainment cue to modulate the molecular clock in NK cells and other spleen cells possibly playing a role in regulating the cytokine and cytolytic function of these cells.
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DOI：
10.1002/cne.22272
发表时间：
2010-04-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Drouyer E;LeSauter J;Hernandez AL;Silver R
通讯作者：
Silver R
DOI：
10.1152/ajpregu.00209.2003
发表时间：
2003-10-01
影响因子：
2.8
作者：
Demas, GE;Bartness, TJ;Drazen, DL
通讯作者：
Drazen, DL
影响因子：
15.1
作者：
BELLINGER, DL;LORTON, D;FELTEN, DL
通讯作者：
FELTEN, DL
影响因子：
15.1
作者：
Arjona, Alvaro;Sarkar, Dipak K.
通讯作者：
Sarkar, Dipak K.
影响因子：
3
作者：
Demas, GE;Bartness, TJ
通讯作者：
Bartness, TJ