The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling
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DOI：
10.1074/jbc.m412584200
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发表时间：
2005-04-29
影响因子：
4.8
通讯作者：
Golenbock, DT
中科院分区：
文献类型：
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作者：
Schoenemeyer, A;Barnes, BJ;Golenbock, DT
干扰素调节因子（IRF）是病毒诱导的免疫激活和I型干扰素调节的关键组分。IRF 3和IRF 7分别响应于多种病毒或在Toll样受体（TLR）3和TLR 4被双链RNA和脂多糖接合后被激活。IRF 5的激活受到更多限制。在这里，我们表明，与IRF 3和IRF 7相反，IRF 5不是TLR 3信号通路的靶点，而是由TLR 7或TLR 8信号通路激活的。我们还证明，MyD 88，白细胞介素1受体相关激酶1，和肿瘤坏死因子受体相关因子6所需的IRF 5和IRF 7的TLR 7信号通路的激活。此外，IRF 5的异位表达使I型干扰素的产生响应于TLR 7信号传导，而通过小干扰RNA敲低IRF 5降低I型干扰素的诱导响应于TLR 7配体R-848。因此，IRF 5和IRF 7从这些研究中作为TLR 7信号传导的关键介质出现。
Interferon regulatory factors (IRFs) are critical components of virus-induced immune activation and type I interferon regulation. IRF3 and IRF7 are activated in response to a variety of viruses or after engagement of Toll-like receptor (TLR) 3 and TLR4 by double-stranded RNA and lipopolysaccharide, respectively. The activation of IRF5, is much more restricted. Here we show that in contrast to IRF3 and IRF7, IRF5 is not a target of the TLR3 signaling pathway but is activated by TLR7 or TLR8 signaling. We also demonstrate that MyD88, interleukin 1 receptor-associated kinase 1, and tumor necrosis factor receptor-associated factor 6 are required for the activation of IRF5 and IRF7 in the TLR7 signaling pathway. Moreover, ectopic expression of IRF5 enabled type I interferon production in response to TLR7 signaling, whereas knockdown of IRF5 by small interfering RNA reduced type I interferon induction in response to the TLR7 ligand, R-848. IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling.