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受睡眠调节的循环人类抗原呈递细胞的数量和功能。

Number and function of circulating human antigen presenting cells regulated by sleep.

作者信息

Dimitrov Stoyan, Lange Tanja, Nohroudi Klaus, Born Jan

机构信息

Department of Neuroendocrinology, University of Lübeck, Germany.

出版信息

Sleep. 2007 Apr;30(4):401-11. doi: 10.1093/sleep/30.4.401.

Abstract

STUDY OBJECTIVES

There is evidence that sleep facilitates the adaptive immune response to infectious agents and, thereby, supports immunologic memory. The effect might be attained by sleep-induced changes in the number and function of dendritic cells (DCs), which play a key role in the initiation of the immune response. This study aimed to dissociate effects of sleep and circadian rhythm on circulating numbers of DC precursors, ie, CD14+CD16- and CD14(dim)CD16+ monocytes, myeloid dendritic cell precursors (pre-mDC), and plasmacytoid dendritic cells (PDC) and on 2 key cytokines produced by these cells, ie, interleukin (IL)-12 and interferon (IFN)-alpha.

DESIGN

In a within-subject cross-over design, human subjects were examined on 2 occasions, ie, during a normal sleep-wake cycle and during 24 hours of wakefulness. Blood was sampled every 1.5 hours during nighttime and every 3 hours during daytime.

SETTING

Experiments took place under controlled laboratory conditions.

PARTICIPANTS

Twenty-seven healthy men aged between 18 and 30 years.

MEASUREMENTS AND RESULTS

Compared with wakefulness, sleep was associated with a striking increase in the number of pre-mDC producing IL-12, which is a main inducer of Th1 responses. In addition, sleep slightly decreased PDC and also T cell counts but did not affect IFN-alpha production by PDC. Sleep, however, substantially decreased numbers of CD14(dim)CD16+ monocytes, probably reflecting increased margination of the cells upon a sleep-related drop in catecholamine release.

CONCLUSIONS

Our data identify pre-mDC producing IL-12 as a basic target of sleep that is most closely related to mature APC function and whereby sleep can effectively enhance adaptive immune responses.

摘要

研究目的

有证据表明,睡眠有助于机体对感染因子产生适应性免疫反应,从而支持免疫记忆。这种作用可能是通过睡眠引起的树突状细胞(DCs)数量和功能的变化来实现的,而树突状细胞在免疫反应的启动中起着关键作用。本研究旨在区分睡眠和昼夜节律对循环中DC前体细胞数量的影响,即CD14+CD16-和CD14(dim)CD16+单核细胞、髓样树突状细胞前体(pre-mDC)和浆细胞样树突状细胞(pDC),以及对这些细胞产生的两种关键细胞因子,即白细胞介素(IL)-12和干扰素(IFN)-α的影响。

设计

采用受试者自身交叉设计,对人类受试者进行了两次检查,即在正常睡眠-觉醒周期和24小时清醒期间。夜间每1.5小时采集一次血液,白天每3小时采集一次。

设置

实验在受控的实验室条件下进行。

参与者

27名年龄在18至30岁之间的健康男性。

测量与结果

与清醒状态相比,睡眠与产生IL-12的pre-mDC数量显著增加有关,IL-12是Th1反应的主要诱导因子。此外,睡眠使pDC和T细胞计数略有下降,但不影响pDC产生IFN-α。然而,睡眠使CD14(dim)CD16+单核细胞数量大幅减少,这可能反映了睡眠相关的儿茶酚胺释放下降导致细胞边缘化增加。

结论

我们的数据确定产生IL-12的pre-mDC是睡眠的一个基本靶点,它与成熟的抗原呈递细胞功能最密切相关,睡眠可通过该靶点有效增强适应性免疫反应。

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