Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression
Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression
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DOI：
10.1073/pnas.0611559104
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发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Taniguchi, Tadatsugu
中科院分区：
文献类型：
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作者：
Yanai, Hideyuki;Chen, Hui-min;Taniguchi, Tadatsugu
宿主防御包括两个主要方面，即对入侵病原体的免疫应答和抑制肿瘤发展。一个转录因子家族，IFN调节因子（ORB），最近因其在连接宿主防御的这两个方面中的关键作用而受到广泛关注，其中IRF 5先前显示在通过激活Toll样受体诱导促炎细胞因子中起关键作用。在本研究中，使用IRF 5基因靶向小鼠（Irf 5（-/-）小鼠），我们证明了IRIF 5在调节免疫应答和肿瘤抑制中的另一个方面的功能。我们表明，IRF 5是至关重要的抗病毒免疫显示Irf 5（-/-）小鼠是非常容易受到病毒感染，伴随着减少I型IFN诱导血清中。此外，我们发现W5- 1成纤维细胞在病毒感染后对凋亡具有抵抗力，从而增强了病毒的繁殖。最后，我们提供的证据表明，IRF 5是诱导细胞凋亡的关键，但不是在细胞周期停滞，在响应DNA损伤和IRF 5作为一个肿瘤抑制因子的作用途径，可能是不同的p53。这些结果，再加上IFN信号和p53对IRF 5基因表达的双重调节，可能为抗病毒免疫和肿瘤抑制的转录网络提供了新的联系。
Host defense consists of two main aspects, namely, immune response to invading pathogens and suppression of tumor development. A family of transcription factors, IFN regulatory factors ORB), has recently gained much attention in terms of its critical role in linking these two aspects of host defense, wherein IRF5 was previously shown to play a critical role in the induction of proinflammatory cytokines by activation of Toll-like receptors. In the present study, using IRF5 gene-targeted mice (Irf5(-/-) mice), we demonstrate another facet of theIRIF5function inthe regulationof immune response and tumor suppression. We show that IRF5 is critical for antiviral immunity by showing that Irf5(-/-) mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that W5-1fibroblasts are resistant to apoptosis upon viral infection, resulting in an enhanced viral propagation. Finally, we provide evidence that IRF5 is critical for the induction of apoptosis, but not in cell cycle arrest, in response to DNA damage and that IRF5 functions as a tumor suppressor by acting on a pathway that may be distinct from that for p53. These results, together with the dual regulation of IRF5 gene expression by IFN signaling and p53, may provide a new link in the transcriptional network underlying antiviral immunity and tumor suppression.