Recognition of DNA is an evolutionarily highly conserved mechanism of immunity. In mammals, the cGAS-STING pathway plays a central role in coupling DNA sensing to the execution of innate immune mechanisms, both in contexts of infection as well as in noninfectious settings of cellular stress and injury. The indiscriminate ability of double-stranded DNA (dsDNA) to activate cGAS challenges our understanding on how engagement of this pathway is prevented on genomic self-DNA under homeostatic conditions. Here, we review recent discoveries on the regulation of cGAS on chromatin and we discuss implications for cGAS-dependent inflammatory phenotypes. We close by highlighting emerging developments on the role of nuclear cGAS and related open questions for future research.

DNA 的识别是一种进化上高度保守的免疫机制。在哺乳动物中，cGAS-STING 通路在将 DNA 传感与先天免疫机制的执行耦合方面发挥着核心作用，无论是在感染环境中还是在细胞应激和损伤的非感染性环境中。双链 DNA (dsDNA) 不加选择地激活 cGAS 的能力挑战了我们对如何在稳态条件下阻止基因组自身 DNA 参与该途径的理解。在这里，我们回顾了最近关于 cGAS 对染色质的调节的发现，并讨论了对 cGAS 依赖性炎症表型的影响。最后，我们重点介绍了有关核 cGAS 作用的新兴发展以及未来研究的相关开放性问题。