干扰素刺激基因STING对I型干扰素的正反馈调节
Positive feedback regulation of type I interferon by the interferon-stimulated gene STING.
作者信息
Ma Feng, Li Bing, Yu Yongxin, Iyer Shankar S, Sun Mingyu, Cheng Genhong
机构信息
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
出版信息
EMBO Rep. 2015 Feb;16(2):202-12. doi: 10.15252/embr.201439366. Epub 2015 Jan 8.
Abstract
Stimulator of interferon genes (STING) is an important regulator of the innate immune response to cytoplasmic DNA. However, regulation of STING itself is largely unknown. Here, we show that STING transcription is induced by innate immune activators, such as cyclic dinucleotides (CDNs), through an IFNAR1- and STAT1-dependent pathway. We also identify a STAT1 binding site in the STING promoter that contributes to the activation of STING transcription. Furthermore, we show that induction of STING mediates the positive feedback regulation of CDN-triggered IFN-I. Thus, our study demonstrates that STING is an interferon-stimulated gene (ISG) and its induction is crucial for the IFN-I positive feedback loop.
摘要
干扰素基因刺激物（STING）是对细胞质DNA先天性免疫反应的重要调节因子。然而，STING自身的调节机制在很大程度上尚不清楚。在此，我们表明STING转录由先天性免疫激活剂如环二核苷酸（CDN）通过IFNAR1和STAT1依赖性途径诱导。我们还在STING启动子中鉴定出一个STAT1结合位点，该位点有助于STING转录的激活。此外，我们表明STING的诱导介导了CDN触发的IFN-I的正反馈调节。因此，我们的研究表明STING是一种干扰素刺激基因（ISG），其诱导对于IFN-I正反馈回路至关重要。
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