Regulation and function of the cGAS-MITA/STING axis in health and disease

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.