{"title":"Regulation of the cGAS-STING Pathway.","authors":"Bing Zhang, Pengbiao Xu, Andrea Ablasser","doi":"10.1146/annurev-immunol-101721-032910","DOIUrl":null,"url":null,"abstract":"<p><p>The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish between self and nonself DNA, cGAS-STING immunity requires precise regulation to prevent aberrant activation. Several safeguard mechanisms acting on different levels have evolved to maintain tolerance to self DNA and ensure immune homeostasis under normal conditions. Disruption of these safeguards can lead to erroneous activation by self DNA, resulting in inflammatory conditions but also favorable antitumor immunity. Insights into structural and cellular checkpoints that control and terminate cGAS-STING signaling are essential for comprehending and manipulating DNA-triggered innate immunity in health and disease.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":" ","pages":""},"PeriodicalIF":26.9000,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-immunol-101721-032910","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The cGAS-cGAMP-STING pathway is essential for immune defense against pathogens. Upon binding DNA, cGAS synthesizes cGAMP, which activates STING, leading to potent innate immune effector responses. However, lacking specific features to distinguish between self and nonself DNA, cGAS-STING immunity requires precise regulation to prevent aberrant activation. Several safeguard mechanisms acting on different levels have evolved to maintain tolerance to self DNA and ensure immune homeostasis under normal conditions. Disruption of these safeguards can lead to erroneous activation by self DNA, resulting in inflammatory conditions but also favorable antitumor immunity. Insights into structural and cellular checkpoints that control and terminate cGAS-STING signaling are essential for comprehending and manipulating DNA-triggered innate immunity in health and disease.
cGAS-cGAMP-STING 通路对于抵御病原体的免疫防御至关重要。结合 DNA 后，cGAS 合成 cGAMP，激活 STING，从而产生强大的先天免疫效应反应。然而，由于 cGAS-STING 免疫缺乏区分自身和非自身 DNA 的特异性，因此需要精确的调控以防止异常激活。为了维持对自身 DNA 的耐受性并确保正常条件下的免疫平衡，已经进化出了几种作用于不同水平的保障机制。破坏这些保障机制会导致自身 DNA 的错误激活，从而引发炎症，但也会产生有利的抗肿瘤免疫。深入了解控制和终止 cGAS-STING 信号传导的结构和细胞检查点，对于理解和操纵 DNA 触发的健康和疾病中的先天免疫至关重要。
期刊介绍：
The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.
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