Transcriptional modulation of the developing immune system by early life social adversity
Transcriptional modulation of the developing immune system by early life social adversity
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DOI：
10.1073/pnas.1218253109
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发表时间：
2012-12-11
影响因子：
11.1
通讯作者：
Suomi, Stephen J.
中科院分区：
文献类型：
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作者：
Cole, Steven W.;Conti, Gabriella;Suomi, Stephen J.
为了确定早期生活的社会条件可能影响成年恒河猴（Macaca mulatta）的疾病风险的分子机制，我们分析了在不利的社会条件下饲养的4个月大的动物的基础白细胞基因表达谱的变化。与基础条件的母亲饲养（MR）相比，白细胞从同伴饲养（PR）动物和PR动物提供了一个无生命的代理母亲（代理/同伴饲养，SPR）显示增强表达的基因参与炎症，细胞因子信号传导，T淋巴细胞活化，抑制基因参与几个先天性抗菌防御，包括I型干扰素（IFN）抗病毒反应。基于启动子的生物信息学分析表明，CREB B和NF-κ B转录因子的活性增加，IFN应答因子（IRF）的活性降低，从而构建了所观察到的基因表达差异。转录起源分析确定单核细胞和CD 4（+）T淋巴细胞是转录上调的主要细胞介质，而B淋巴细胞是下调基因的主要来源。这些发现表明，不利的社会条件可以在生命的前4个月内嵌入灵长类免疫细胞的基础转录组中，并且它们涉及交感神经系统相关的转录控制途径作为这些影响的候选介质和健康保护干预的潜在目标。
To identify molecular mechanisms by which early life social conditions might influence adult risk of disease in rhesus macaques (Macaca mulatta), we analyze changes in basal leukocyte gene expression profiles in 4-mo-old animals reared under adverse social conditions. Compared with the basal condition of maternal rearing (MR), leukocytes from peer-reared (PR) animals and PR animals provided with an inanimate surrogate mother (surrogate/peer reared, SPR) show enhanced expression of genes involved in inflammation, cytokine signaling, and T-lymphocyte activation, and suppression of genes involved in several innate antimicrobial defenses including type I interferon (IFN) antiviral responses. Promoter-based bioinformatic analyses implicate increased activity of CREB and NF-kappa B transcription factors and decreased activity of IFN response factors (IRFs) in structuring the observed differences in gene expression. Transcript origin analyses identify monocytes and CD4(+) T lymphocytes as primary cellular mediators of transcriptional up-regulation and B lymphocytes as major sources of down-regulated genes. These findings show that adverse social conditions can become embedded within the basal transcriptome of primate immune cells within the first 4 mo of life, and they implicate sympathetic nervous system-linked transcription control pathways as candidate mediators of those effects and potential targets for health-protective intervention.