The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING
The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING
复制标题
环肽 Astin C 特异性抑制先天免疫 CDN 传感器 STING
DOI：
10.1016/j.celrep.2018.11.097
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发表时间：
2018-12-18
期刊：
影响因子：
8.8
通讯作者：
Wang, Chen
中科院分区：
文献类型：
--
作者：
Li, Senlin;Hong, Ze;Wang, Chen
cGAS-STING信号传导对先天免疫至关重要。它的错误调节促进癌症或自身免疫性和自身炎症性疾病，并且必须确定特异性下调该途径的有效先导化合物。我们在这里报告，astin C，一种从药用植物紫菀中分离的环肽，抑制cGAS-STING信号传导和由胞质DNA引发的先天性炎症反应。此外，用astin C治疗的小鼠更容易感染HSV-1。一致地，astin C显著减弱Trex 1（-/-）BMDM细胞和Trex 1（-/-）小鼠自身免疫性疾病模型中的自身炎症反应。在机制上，astin C特异性地阻断IRF 3募集到STING信号体上。总的来说，本研究表征了一种STING特异性小分子抑制剂，其可用于潜在地操纵STING介导的临床疾病。
cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1(-/-) BMDM cells and in Trex1(-/-) mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.