Matsui Kosuke, Kumagai Yutaro, Kato Hiroki, Sato Shintaro, Kawagoe Tatsukata, Uematsu Satoshi, Takeuchi Osamu, Akira Shizuo
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
J Immunol. 2006 Nov 1;177(9):5785-9. doi: 10.4049/jimmunol.177.9.5785.
TANK-binding kinase 1 (TBK1) and inducible IkappaB kinase (IKK-i) are involved in the activation of transcription factors inducing the production of type I IFNs. Although TBK1, but not IKK-i, is critical for LPS-induced IFN induction, the role of these kinases in the responses against viral infection is yet to be determined. In this study, we show that type I IFN production against various RNA viruses was completely abrogated in conventional dendritic cells (DCs) and macrophages induced from fetal liver cells lacking both TBK1 and IKK-i, whereas considerable amounts of IFN were produced in cells lacking either of them. Microarray analysis revealed that various IFN-inducible genes were also regulated by the kinases. In contrast, Fms-like tyrosine kinase 3 ligand-induced DCs produced IFN-alpha even in the absence of both TBK1 and IKK-i. Thus, these two kinases are essential and compensate each other for the regulation of IFN responses in innate immune cells except plasmacytoid DCs.
TANK结合激酶1（TBK1）和诱导性κB激酶（IKK-i）参与诱导I型干扰素产生的转录因子的激活。尽管TBK1而非IKK-i对LPS诱导的干扰素诱导至关重要，但这些激酶在抗病毒感染反应中的作用尚待确定。在本研究中，我们发现，在缺乏TBK1和IKK-i的胎儿肝细胞诱导产生的常规树突状细胞（DCs）和巨噬细胞中，针对各种RNA病毒的I型干扰素产生完全被消除，而在缺乏其中任何一种的细胞中则产生大量干扰素。微阵列分析显示，各种干扰素诱导基因也受这些激酶调控。相比之下，即使在缺乏TBK1和IKK-i的情况下，Fms样酪氨酸激酶3配体诱导的DCs仍能产生干扰素-α。因此，这两种激酶对于除浆细胞样DCs外的先天免疫细胞中干扰素反应的调节至关重要且相互补偿。
