Blockade of mineralocorticoid receptors enhances naive T-helper cell counts during early sleep in humans
Blockade of mineralocorticoid receptors enhances naive T-helper cell counts during early sleep in humans
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DOI：
10.1016/j.bbi.2012.07.016
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发表时间：
2012-10-01
影响因子：
15.1
通讯作者：
Lange, Tanja
中科院分区：
文献类型：
--
作者：
Besedovsky, Luciana;Born, Jan;Lange, Tanja
睡眠支持免疫记忆的形成，如受试者在随后的夜晚睡觉比保持清醒时对疫苗接种的免疫应答更强所证明的。睡眠的这种类似催眠的作用的一个机制可能是循环的幼稚T细胞向淋巴结的归巢增强。事实上，与夜间觉醒相比，睡眠在夜间早期急剧降低外周血中的T细胞计数，这些细胞流出淋巴组织可能是由睡眠相关的盐皮质激素醛固酮释放介导的。我们在这里表明，在11名健康男性中，通过螺内酯（200 mg，口服，23：00 h和4：00 h）阻断盐皮质激素受体可增强夜间睡眠早期血液中的幼稚辅助性T细胞计数。在相同方向上对幼稚细胞毒性T细胞和中枢记忆辅助性T细胞的影响不太一致。螺内酯不影响不迁移到淋巴结的T细胞亚群（即，CD 62 L（-）效应记忆和效应T细胞）或CD 62 L和CXCR 4的表达。T细胞数量在早晨的典型昼夜节律减少不受盐皮质激素受体阻断的影响，这与以下观点一致，即这种减少主要是由于皮质醇在昼夜节律早晨上升期间糖皮质激素受体的激活。我们假设，睡眠相关的激活盐皮质激素受体在低皮质醇水平的时间有助于增强再分配循环幼稚T辅助细胞淋巴结，作为一种机制，最终促进免疫记忆的形成。(c)2012 Elsevier Inc. All rights reserved.
Sleep supports the formation of immunological memory as evidenced by a stronger immune response to vaccination if subjects sleep during the subsequent night than if they stay awake. One mechanism underlying this adjuvant-like action of sleep might be an enhanced homing of circulating naive T cells to lymph nodes. Indeed, compared to nocturnal wakefulness, sleep acutely lowers T cell counts in peripheral blood during the early night, with the efflux of these cells to lymphoid tissues possibly mediated by sleep-associated release of the mineralocorticoid aldosterone. We show here that blocking mineralocorticoid receptors by spironolactone (200 mg, orally at 23:00 h and again at 4:00 h) in 11 healthy men enhances naive T-helper cell counts in blood during early nocturnal sleep. Effects in the same direction on naive cytotoxic T cells and central memory T-helper cells were less consistent. Spironolactone did not influence T cell subsets not migrating to lymph nodes (i.e., CD62L(-) effector memory and effector T cells), or expression of CD62L and CXCR4. The typical circadian decrease in T cell numbers in the morning hours was not affected by the blockade of mineralocorticoid receptors, in line with the view that this decrease is mainly due to activation of glucocorticoid receptors during the circadian morning rise in cortisol. We assume that sleep-associated activation of mineralocorticoid receptors at a time of low cortisol levels contributes to an enhanced redistribution of circulating naive T-helper cells to lymph nodes, as a mechanism that eventually promotes immunological memory formation. (c) 2012 Elsevier Inc. All rights reserved.