Glucocorticoid receptor signaling in leukocytes after early life adversity
Glucocorticoid receptor signaling in leukocytes after early life adversity
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DOI：
10.1017/s0954579419001147
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发表时间：
2020-08-01
影响因子：
3.3
通讯作者：
Turner, Jonathan D.
中科院分区：
文献类型：
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作者：
Elwenspoek, Martha M. C.;Hengesch, Xenia;Turner, Jonathan D.
早年逆境 (ELA) 与炎症和免疫衰老以及 HPA 轴反应性低下有关。由于免疫系统和 HPA 轴与糖皮质激素受体 (GR) 紧密相连，因此我们在 EpiPath 队列中检查了暴露于 ELA（与父母分离和/或收容后收养；n = 40）或由其亲生父母抚养（n = 72）的参与者的外周 GR 功能。严格GR靶基因FKBP5和GILZ以及总转录本和1F和1HGR转录本的表达在组间相似。此外，通过地塞米松对 LPS 刺激的全血中 IL6 产生的影响来检查，GR 敏感性没有差异。尽管我们没有发现 GR1Fexon 或启动子区域的甲基化差异，但我们鉴定了 GR1H 启动子 (CpG 1-9) 的一个区域，该区域在 ELA 中显示出较低的甲基化水平。我们的结果表明，在我们的队列中，外周 GR 信号传导未受到干扰，并且观察到的免疫表型似乎并不是继发于对受干扰的 HPA 轴和糖皮质激素 (GC) 谱的 GR 反应改变，尽管我们对 GR 活性和时间点的测量受到限制。
Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption;n= 40) or had been reared by their biological parents (n= 72). Expression of the strict GR target genesFKBP5andGILZas well as total and1Fand1HGR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR1Fexon or promoter region, we identified a region of the GR1Hpromoter (CpG 1-9) that showed lower methylation levels in ELA. Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.