The presence of DNA in the cytosol is usually a sign of microbial infections, which alerts the host innate immune system to mount a defense response. Cyclic GMP‐AMP synthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate immune responses through the production of the second messenger, cyclic GMP‐AMP (cGAMP), which binds and activates stimulator of interferon genes (STING). However, cGAS binds to DNA irrespective of DNA sequence, therefore, self‐DNA leaked from the nucleus or mitochondria can also serve as a cGAS ligand to activate this pathway and trigger extensive inflammatory responses. Dysregulation of the cGAS‐STING pathway is responsible for a broad array of inflammatory and autoimmune diseases. Recently, evidence has shown that self‐DNA release and cGAS‐STING pathway over‐activation can drive lung disease, making this pathway a promising therapeutic target for inflammatory lung disease. Here, we review recent advances on the cGAS‐STING pathway governing self‐DNA sensing, highlighting its role in pulmonary disease.

中文翻译：

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cGAS-STING 通路：自身 DNA 传感在炎症性肺病中的作用

细胞质中 DNA 的存在通常是微生物感染的征兆，它会提醒宿主先天免疫系统进行防御反应。环状 GMP-AMP 合酶 (cGAS) 是一种关键的细胞溶质 DNA 传感器，可通过产生第二信使环状 GMP-AMP (cGAMP) 来引发强大的先天免疫反应，该第二信使可结合并激活干扰素基因 (STING) 的刺激物。然而，cGAS 与 DNA 结合与 DNA 序列无关，因此，从细胞核或线粒体泄漏的自身 DNA 也可以作为 cGAS 配体激活该途径并引发广泛的炎症反应。cGAS-STING 通路的失调是导致多种炎症和自身免疫疾病的原因。最近，有证据表明，自身 DNA 释放和 cGAS-STING 通路过度激活会导致肺部疾病，使该途径成为炎症性肺病的有希望的治疗靶点。在这里，我们回顾了控制自身 DNA 传感的 cGAS-STING 通路的最新进展，强调了它在肺部疾病中的作用。