Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

中文翻译：

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肯尼亚健康成人和儿童单核细胞 DNA 甲基化和免疫功能的年龄相关差异

适应性和先天免疫细胞的年龄相关变化与有效免疫力下降和慢性低度炎症有关。单核细胞的表观遗传、转录和功能变化会随着年龄的增长而发生，尽管迄今为止的大多数研究都集中在欧洲血统人群中年轻人和老年人之间的差异。关于生命最初几十年或非洲人群中循环单核细胞发生变化的数据很少。我们分析了来自肯尼亚西部的年轻人和儿童的单核细胞中的 DNA 甲基化谱、细胞因子产生和炎症基因表达谱。我们在来自肯尼亚年轻成人和年轻成人的单核细胞中鉴定了几个低甲基化和高甲基化的 CpG 位点。儿童复制了当前文献中老年人与不同人群的年轻人单核细胞中差异 DNA 甲基化的发现。在对炎症和先天免疫反应很重要的基因区域中也注意到了差异甲基化的 CpG 位点。来自肯尼亚年轻成人和儿童的单核细胞显示出响应 TLR4 和 TLR2/1 刺激以及不同的炎症基因表达谱的 IL-8、IL-10 和 IL-12p70 产量增加。这些发现补充了先前关于分离的单核细胞中与年龄相关的甲基化变化的报告，并提供了对年龄相关变化在先天免疫功能中的作用的新见解。在对炎症和先天免疫反应很重要的基因区域中也注意到了差异甲基化的 CpG 位点。来自肯尼亚年轻成人和儿童的单核细胞显示出响应 TLR4 和 TLR2/1 刺激以及不同的炎症基因表达谱的 IL-8、IL-10 和 IL-12p70 产量增加。这些发现补充了先前关于分离的单核细胞中与年龄相关的甲基化变化的报告，并提供了对年龄相关变化在先天免疫功能中的作用的新见解。在对炎症和先天免疫反应很重要的基因区域中也注意到了差异甲基化的 CpG 位点。来自肯尼亚年轻成人和儿童的单核细胞显示出响应 TLR4 和 TLR2/1 刺激以及不同的炎症基因表达谱的 IL-8、IL-10 和 IL-12p70 产量增加。这些发现补充了先前关于分离的单核细胞中与年龄相关的甲基化变化的报告，并提供了对年龄相关变化在先天免疫功能中的作用的新见解。