Abstract：
Analysis of genetically defined immunodeficient patients allows study of the effect of the absence of specific proteins on human immune function in real-world conditions. Here we have addressed the importance of type I interferon signalling for human NK cell development by studying the phenotype and function of circulating NK cells isolated from patients suffering primary immunodeficiency disease due to mutation of either the human interferon regulatory factor 9 (IRF9) or the signal transducer and activator of transcription 2 (STAT2) genes. IRF9, together with phosphorylated STAT1 and STAT2, form a heterotrimer called interferon stimulated gene factor 3 (ISGF3) which promotes the expression of hundreds of IFN-stimulated genes that mediate antiviral function triggered by exposure to type I interferons. IRF9- and STAT2-deficient patients are unable to respond efficiently to stimulation by type I interferons and so our experiments provide insights into the importance of type I interferon signalling and the consequences of its impairment on human NK cell biology. Surprisingly, the NK cells of these patients display essentially normal phenotype and function.
摘要：
对遗传定义的免疫缺陷患者的分析可以研究在现实条件下缺乏特定蛋白质对人类免疫功能的影响。在这里，我们已经通过研究从患有原发性免疫缺陷疾病的患者中分离的循环NK细胞的表型和功能，解决了I型干扰素信号传导对于人NK细胞发育的重要性。由于人干扰素调节因子9（IRF9）或信号转导和转录激活因子2（STAT2）基因的突变。IRF9与磷酸化的STAT1和STAT2一起形成称为干扰素刺激基因因子3（ISGF3）的异源三聚体，可促进数百种IFN刺激基因的表达，这些基因介导由暴露于I型干扰素触发的抗病毒功能。IRF9和STAT2缺陷患者无法有效地响应I型干扰素的刺激，因此我们的实验提供了对I型干扰素信号传导的重要性及其对人NK细胞生物学损伤的后果的见解。令人惊讶的是,这些患者的NK细胞表现出基本正常的表型和功能。
