Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex
Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex
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DOI：
10.1089/jir.2005.25.770
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发表时间：
2005-12-01
影响因子：
2.3
通讯作者：
Ozato, K
中科院分区：
文献类型：
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作者：
Kanno, Y;Levi, BZ;Ozato, K
I型干扰素（IFN-α/β）和II型干扰素（IFN-γ）都发挥许多仅限于免疫细胞的功能。因此，它们在先天性和适应性免疫中发挥关键作用。IFN调节因子-4（IRF-4）和IRF-8（以前称为PU. 1相互作用配偶体[ Pip]和IFN共有序列结合结构域[ ICSBP]）是IRF家族的免疫细胞特异性成员，其调节骨髓、淋巴和树突细胞的发育。它们与另一种免疫细胞特异性转录因子PU形成异二聚体复合物。1-Spi-1和调节免疫系统中基因的转录。本文综述了IRF-8-PU.1复合物在以免疫细胞特异性方式调节IFN信号传导中的作用。我们的研究表明，一些但不是所有的IFN-γ诱导基因携带IFN-γ激活位点（GAS）元件，该元件含有IRF 8-PU.1复合物的结合位点。IRF-8-PU.1复合物可参与GAS介导的转录，并扩增巨噬细胞中由Stat 1启动的IFN-γ应答基因的表达。类似地，一些但不是所有的IFN-α/β应答基因显示携带含有IRF-8-PU.1结合位点的IFN刺激应答元件（ISRE）。IRF-8-PU.1参与ISRE介导的转录导致巨噬细胞中IFN刺激的基因因子3（ISGF 3）诱导的转录增强。因此，GAS和ISRE元件，经典地定义为通用IFN-α/β和IFN-γ应答序列，是不相同的，并且一些具有IRF 8-PU的嵌入基序。1结合，仅在免疫细胞中起作用。因此，IRF-8-PU.1复合物提供了免疫系统特有的次级IFN信号传导途径。IRF-8和PU共同作出贡献。1至IFN调节的基因表达可能部分解释了IFN的免疫细胞特异性功能。
Both type I interferon (IFN-alpha/beta) and type II IFN ( IFN-gamma) exert many functions that are restricted to immune cells. Thus, they play critical roles in innate and adaptive immunity. IFN regulatory factor-4 (IRF-4) and IRF-8 ( formerly PU. 1 interaction partner [ Pip] and IFN consensus sequence binding domain [ ICSBP], respectively) are immune cell-specific members of the IRF family that regulate the development of myeloid, lymphoid, and dendritic cells. They form a heterodimeric complex with another immune cell-specific transcription factor PU. 1-Spi-1 and regulate transcription of genes in the immune system. This review describes the role of the IRF-8-PU.1 complex in modulating IFN signaling in an immune cell-specific manner. Our studies revealed that some but not all IFN-gamma-inducible genes carry an IFN-gamma activation site ( GAS) element that contains a binding site for the IRF8-PU.1 complex. The IRF-8-PU.1 complex can take part in GAS-mediated transcription and amplify expression of IFN-gamma-responsive genes initiated by Stat1 in macrophages. Similarly, some but not all IFN-alpha/beta-responsive genes are shown to carry an IFN-stimulated response element ( ISRE) that contains an IRF-8-PU.1 binding site. The participation of IRF-8-PU.1 in ISRE-mediated transcription results in the augmentation of IFN-stimulated gene factor 3 ( ISGF3)-induced transcription in macrophages. Thus, GAS and ISRE elements, classically defined as universal IFN-alpha/beta and IFN-gamma response sequences, are not the same, and some harbor an embedded motif for IRF8-PU. 1 binding that functions only in immune cells. Accordingly, the IRF-8-PU.1 complex provides secondary IFN signaling pathways unique to the immune system. Collectively, the contribution of IRF-8 and PU. 1 to IFN-regulated gene expression may in part account for immune cell-specific functions of IFNs.