The cGAS‐STING pathway: The role of self‐DNA sensing in inflammatory lung disease

The presence of DNA in the cytosol is usually a sign of microbial infections, whichalerts the host innate immune system to mount a defense response. Cyclic GMP-AMPsynthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate im-mune 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 fromthe nucleus or mitochondria can also serve as a cGAS ligand to activate this pathwayand trigger extensive inflammatory responses. Dysregulation of the cGAS-STINGpathway 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 targetfor inflammatory lung disease. Here, we review recent advances on the cGAS-STINGpathway governing self-DNA sensing, highlighting its role in pulmonary disease.

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Published in: The FASEB Journal
License: http://creativecommons.org/licenses/by-nc/4.0/
See article on publisher's website: https://dx.doi.org/10.1096/fj.202001607r