Journal Article

Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing

Chen, Qi, Sun, Lijun, Chen, Zhijian J

2016

Overview

In this Review, Chen and colleagues discuss recent advances in understanding of the cGAS–STING pathway, focusing on the regulatory mechanisms and roles of this pathway in heath and disease. The recognition of microbial nucleic acids is a major mechanism by which the immune system detects pathogens. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger cGAMP, which activates the adaptor STING. The cGAS–STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity. However, aberrant activation of the cGAS pathway by self DNA can also lead to autoimmune and inflammatory disease. Thus, the cGAS pathway must be properly regulated. Here we review the recent advances in understanding of the cGAS–STING pathway, focusing on the regulatory mechanisms and roles of this pathway in heath and disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/254 / 631/250/262 / Animals / Autoimmunity / Biomedicine / Cyclic AMP - metabolism / Cyclic GMP / Cyclic guanosine monophosphate / Cytosol - metabolism / Deoxyribonucleic acid / DNA / DNA - immunology / DNA identification / Genetic aspects / Host-Pathogen Interactions / Humans / Immune response / Immune system / Immunity, Innate / Immunologic Surveillance / Immunology / Infections - immunology / Infectious Diseases / Inflammation / Inflammatory diseases / Innate immunity / Membrane Proteins - metabolism / Methods / Neoplasms - immunology / Nucleic acids / Nucleotidyltransferases - metabolism / Pathogens / Physiological aspects / review-article / Signal Transduction / Tumors