Ane Calvo-Apalategi, Marta López Nevado, Luz Yadira Bravo-Gallego, Luis Ignacio González-Granado, Luis M. Allende, Rebeca Rodríguez Pena, Eduardo López-Granados, Hugh T. Reyburn
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引用次数: 0
摘要
通过对基因界定的免疫缺陷患者进行分析,可以研究在真实世界条件下缺乏特定蛋白质对人体免疫功能的影响。在这里,我们通过研究从因人类干扰素调节因子9(IRF9)或转录信号转导和激活因子2(STAT2)基因突变而患原发性免疫缺陷病患者体内分离出来的循环NK细胞的表型和功能,探讨了I型干扰素信号对人类NK细胞发育的重要性。IRF9与磷酸化的STAT1和STAT2一起,形成了一种称为干扰素刺激基因因子3(ISGF3)的异源三聚体,它能促进数百个IFN刺激基因的表达,这些基因介导因暴露于I型干扰素而触发的抗病毒功能。IRF9和STAT2缺陷患者无法对I型干扰素的刺激做出有效反应,因此我们的实验让人们深入了解了I型干扰素信号的重要性及其对人类NK细胞生物学的影响。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。
The lack of either IRF9, or STAT2, has surprisingly little effect on human natural killer cell development and function
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.
期刊介绍:
Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers.
Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology.
The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.