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腾讯登录Science：两项研究解码遗传变异如何影响免疫细胞
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日前，《科学》（Science）杂志刊登了两项关于人类免疫细胞的论文，研究人员解析了遗传变异如何影响免疫细胞中的基因表达，并指出这些细胞的周边环境在免疫应答过程中扮演了何种角色。在第一项研究中，来自牛津大学，剑桥大学等机构的研究人员令人类单核细胞接触相似的病原体相关分子，由此绘制出了这些细胞中与表达有关的遗传突变图谱。这对于免疫功能性遗传突变研究具有... |
日前，《科学》（Science）杂志刊登了两项关于人类免疫细胞的论文，研究人员解析了遗传变异如何影响免疫细胞中的基因表达，并指出这些细胞的周边环境在免疫应答过程中扮演了何种角色。
在第一项研究中，来自牛津大学，剑桥大学等机构的研究人员令人类单核细胞接触相似的病原体相关分子，由此绘制出了这些细胞中与表达有关的遗传突变图谱。这对于免疫功能性遗传突变研究具有重要意义。研究人员先收集了来自 432 位健康欧洲人的原代单核细胞，并用 interferon-g（IFN-g），或者不同浓度的脂多糖进行处理，从而绘制出了表达数量性状遗传位点（expression quantitative trait loci, eQTLs）图谱。eQTLs 是指一些能调节基因表达水平的位点，eQTL作图法可揭示众多单核苷酸多态（single nucleotide polymorphisms, SNPs）的未知生物学功能。
在第二项研究则由哈佛大学医学院等机构的研究人员完成，他们分析树突状细胞接触大肠杆菌和流感病毒等分子后的反应，解析与表达有关的遗传突变如何在这些细胞中产生影响的。关于人类遗传突变如何影响复杂疾病对环境刺激的应答，至今科学家们知道的很少。在这项研究中，研究人员识别出了 121 个常见的相关遗传突变，涉及对大肠杆菌脂多糖，流感，或interferon-b (IFN-b)分子的应答。由此揭示了关于免疫疾病易感性的一些相关信息。
这两项研究中进一步增进了研究人员对于个体免疫应答的理解，解析了个体对于免疫威胁的应答差异，以及对于复杂疾病的易感性。
原文链接：Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
abstract
Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses toEscherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.
Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression
abstract
To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor–modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.
来源：bio360
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