The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.

Abstract

The cGAS-STING pathway is a critical signaling mechanism in the innate immune system for sensing cytosolic DNA and subsequently facilitating antiviral responses. Cyclic GMP-AMP synthase (cGAS) recognizes both foreign and self-DNA in the cytosol, resulting in the formation of 2'3'-cyclic GMP-AMP. STING is activated by the cyclic dinucleotide and drives the production of type I interferons as well as pro-inflammatory cytokines. Generating an inflammatory response through the cGAS-STING pathway is critical for antiviral defense, and this cascade also has been involved in the regulation of autophagy, cellular senescence, and other diseases. Defects in this pathway can result in autoimmunity, chronic inflammation, or increased cancer susceptibility. The molecular mechanisms underlying this pathway, its regulatory factors, and how it may contribute to diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and certain cancers were reviewed. This review further covers the therapeutic approaches to this system, such as agonists for cancer treatment and antagonists for autoimmune diseases.