Zhang Zhi-Dong, Zhong Bo
Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Cell Insight. 2022 Jan 5;1(1):100001. doi: 10.1016/j.cellin.2021.100001. eCollection 2022 Feb.
The innate immune systems detect pathogens via pattern-recognition receptors including nucleic acid sensors and non-nucleic acid sensors. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS, also known as MB21D1) is a cytosolic DNA sensor that recognizes double-stranded DNA (dsDNA) and catalyzes the synthesis of 2',3'-cGAMP. Subsequently, 2',3'-cGAMP binds to the adaptor protein mediator of IRF3 activation (MITA, also known as STING, MPYS, ERIS, and TMEM173) to activate downstream signaling cascades. The cGAS-MITA/STING signaling critically mediates immune responses against DNA viruses, retroviruses, bacteria, and protozoan parasites. In addition, recent discoveries have extended our understanding of the roles of the cGAS-MITA/STING pathway in autoimmune diseases and cancers. Here, we summarize the identification and activation of cGAS and MITA/STING, present the updated functions and regulatory mechanisms of cGAS-MITA/STING signaling and provide a comprehensive understanding of the cGAS-MITA/STING axis in autoimmune diseases and cancers.
固有免疫系统通过模式识别受体（包括核酸传感器和非核酸传感器）来检测病原体。环磷酸鸟苷-腺苷酸合成酶（cGAS，也称为MB21D1）是一种胞质DNA传感器，可识别双链DNA（dsDNA）并催化2',3'-环磷酸鸟苷-腺苷酸（2',3'-cGAMP）的合成。随后，2',3'-cGAMP与干扰素调节因子3激活的衔接蛋白介质（MITA，也称为STING、MPYS、ERIS和TMEM173）结合，以激活下游信号级联反应。cGAS-MITA/STING信号通路在介导针对DNA病毒、逆转录病毒、细菌和原生动物寄生虫的免疫反应中起关键作用。此外，最近的发现扩展了我们对cGAS-MITA/STING通路在自身免疫性疾病和癌症中作用的理解。在此，我们总结了cGAS和MITA/STING的鉴定与激活过程，介绍了cGAS-MITA/STING信号通路的最新功能和调控机制，并全面阐述了其在自身免疫性疾病和癌症中的作用。
