STING: infection, inflammation and cancer.
STING: infection, inflammation and cancer.
复制标题
DOI：
10.1038/nri3921
复制
发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
干扰素基因刺激因子（STING）通过与环状二核苷酸（CDN）结合而被激活，这导致有效的细胞因子产生。CDN由某些细胞内细菌产生，并且由环状GMP-AMP合酶（cGAS）在与细胞溶质DNA物质（例如病毒DNA）结合后产生。STING诱导的先天免疫分子对于保护宿主免受病原体侵害是必不可少的，并且对于刺激适应性免疫是重要的。自身DNA，例如来自细胞核或线粒体的DNA，可以泄漏到细胞质区室并刺激STING活性，导致自身炎症性疾病。编码STING的基因中的某些突变可以导致蛋白质变得永久活跃，并类似地诱导自身炎症反应。STING可以在吞噬细胞中被吞噬的肿瘤细胞释放的DNA激活，并驱动产生强大的抗肿瘤T细胞反应所必需的细胞因子的产生。DNA损伤剂可导致细胞核DNA释放到细胞质中，刺激STING依赖性细胞因子产生和吞噬细胞浸润。这可能是消除受损细胞和产生抗肿瘤T细胞反应所必需的，但慢性刺激也可能促进炎症加重癌症。STING激动剂发挥有效的抗肿瘤活性，可能是疫苗制剂中有效的新型佐剂。相比之下，STING信号传导的抑制剂可能有益于治疗自身炎症性疾病，如系统性红斑狼疮（SLE），Aicardi-Goutières综合征（AGS）和婴儿期发作的STING相关血管病变（SAVI）。本文的在线版本（doi：10.1038/nri 3921）包含补充材料，可供授权用户使用。通过胞质异常DNA种类或环状二核苷酸激活STING（干扰素基因的刺激物）触发许多先天免疫基因的转录。在这篇综述中，作者总结了最近对STING信号调节及其在自身炎症性疾病和癌症中的作用的见解。本文的在线版本（doi：10.1038/nri 3921）包含补充材料，可供授权用户使用。微生物病原体的快速检测对于有效启动宿主抗感染防御机制至关重要。了解细胞如何检测胞质DNA以触发先天免疫基因转录具有重要意义-不仅对于理解对病原体的免疫应答，而且对于阐明涉及自身DNA传感的自身炎性疾病的原因以及有效的抗肿瘤适应性免疫的产生。STING（干扰素基因刺激因子）控制的先天免疫途径（介导细胞溶质DNA诱导的信号传导事件）的发现最近为这些过程提供了重要的见解，为开发新型免疫方案以及治疗自身炎症性疾病和癌症的疗法开辟了道路。本文的在线版本（doi：10.1038/nri 3921）包含补充材料，可供授权用户使用。
Stimulator of interferon genes (STING) is activated by binding to cyclic dinucleotides (CDNs), which results in potent cytokine production. CDNs are produced by certain intracellular bacteria and are generated by the cyclic GMP–AMP synthase (cGAS) following binding to cytosolic DNA species, such as viral DNA. STING-inducible innate immune molecules are essential for protection of the host against pathogens and are important for the stimulation of adaptive immunity. Self-DNA, for example from the nucleus or mitochondria, can leak into the cytosolic compartment and stimulate STING activity to cause autoinflammatory disease. Certain mutations in the gene encoding STING can cause the protein to become permanently active and similarly induce autoinflammatory responses. STING can be activated in phagocytes by DNA released from engulfed tumour cells and drive the production of cytokines necessary for generating robust antitumour T cell responses. DNA-damaging agents can cause the release of nuclear DNA into the cytosol that stimulates STING-dependent cytokine production and phagocyte infiltration. This may be essential for eliminating damaged cells and generating antitumour T cell responses, but chronic stimulation may also promote inflammation-aggravated cancer. STING agonists exert potent antitumour activity and may be effective, novel adjuvants in vaccine formulations. In contrast, inhibitors of STING signalling may be beneficial for the treatment of autoinflammatory disease, such as systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS) and STING-associated vasculopathy with onset in infancy (SAVI). The online version of this article (doi:10.1038/nri3921) contains supplementary material, which is available to authorized users. Activation of STING (stimulator of interferon genes) by cytosolic aberrant DNA species or cyclic dinucleotides triggers transcription of numerous innate immune genes. In this Review, the author summarizes recent insights into the regulation of STING signalling and its role in autoinflammatory disease and cancer. The online version of this article (doi:10.1038/nri3921) contains supplementary material, which is available to authorized users. The rapid detection of microbial agents is essential for the effective initiation of host defence mechanisms against infection. Understanding how cells detect cytosolic DNA to trigger innate immune gene transcription has important implications — not only for comprehending the immune response to pathogens but also for elucidating the causes of autoinflammatory disease involving the sensing of self-DNA and the generation of effective antitumour adaptive immunity. The discovery of the STING (stimulator of interferon genes)-controlled innate immune pathway, which mediates cytosolic DNA-induced signalling events, has recently provided important insights into these processes, opening the way for the development of novel immunization regimes, as well as therapies to treat autoinflammatory disease and cancer. The online version of this article (doi:10.1038/nri3921) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
8.8
作者：
Corrales L;Glickman LH;McWhirter SM;Kanne DB;Sivick KE;Katibah GE;Woo SR;Lemmens E;Banda T;Leong JJ;Metchette K;Dubensky TW Jr;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
32.4
作者：
Gall A;Treuting P;Elkon KB;Loo YM;Gale M Jr;Barber GN;Stetson DB
通讯作者：
Stetson DB
影响因子：
6.7
作者：
Archer KA;Durack J;Portnoy DA
通讯作者：
Portnoy DA
影响因子：
17.1
作者：
Fu J;Kanne DB;Leong M;Glickman LH;McWhirter SM;Lemmens E;Mechette K;Leong JJ;Lauer P;Liu W;Sivick KE;Zeng Q;Soares KC;Zheng L;Portnoy DA;Woodward JJ;Pardoll DM;Dubensky TW Jr;Kim Y
通讯作者：
Kim Y
影响因子：
30.5
作者：
通讯作者：
--