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Intervention of cGAS‒STING signaling in sterile inflammatory diseases
Ze Hong1,† , Jiahao Mei1,† , Hanli Guo1 , Juanjuan Zhu1,* , Chen Wang1,*
1State Key Laboratory of Natural Medicines, Department of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
These authors contributed equally to this work
*Correspondence to:Juanjuan Zhu , Chen Wang ,
J Mol Cell Biol, Volume 14, Issue 2, February 2022, mjac005,
Keyword: GAS, STING, DNA, sterile inflammatory disease, antagonist

Sterile inflammation characterized by unresolved chronic inflammation is well established to promote the progression of multiple autoimmune diseases, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, collectively termed ‘sterile inflammatory diseases’. By recognizing host-derived DNA, cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) activates endoplasmic reticulum-associated stimulator of interferon genes (STING), which leads to the induction of type I interferons and inflammatory cytokines or immunogenic cell death that promotes sterile inflammation. Additionally, the DNA/cGAS-independent mode of STING activation has also been characterized in the progression of several sterile inflammatory diseases. This review focuses on the molecular mechanism of cGAS-dependent and cGAS-independent STING signaling under various disease conditions, particularly highlighting the diverse initiators upon this signaling pathway. We also summarize recent advances in the discovery of antagonists targeting cGAS and STING and the evaluation of their efficiencies in preclinical models. Finally, we discuss potential differences in the clinical applications of the specific antagonists, which may shed light on the precision therapeutic interventions.