Abstract
DNA immune recognition regulation mediated by the cGAS-STING pathway plays an important role in immune functions. Under normal physiological conditions, cGAS can recognize and bind to invading pathogen DNA and activate the innate immune response. On the other hand, abnormal activation of cGAS or STING is closely related to autoimmune diseases. In addition, activation of STING proteins as a bridge connecting innate immunity and adaptive immunity can effectively restrain tumor growth. Therefore, targeting the cGAS-STING pathway can alleviate autoimmune symptoms and be a potential drug target for treating cancer. This article summarizes the current progress on cGAS-STING pathway modulators and lays the foundation for further investigating therapeutic development in autoimmune diseases and tumors.
Highlights
Innate Immunity and Immune DiseasesInnate Immunity and cGAMP synthase (cGAS)-STING Signaling Pathway The human immune system uses pattern recognition to sense infection and trigger an immune response against pathogen invasion
It was found that the function of STING was strictly regulated by membrane transport, and retrograde membrane transport was crucial for silencing signaling pathways
Using the regulatory agents to target membrane transport is likely to be a novel strategy for treating autoimmune diseases (Taguchi et al, 2021)
Summary
Innate Immunity and cGAS-STING Signaling Pathway The human immune system uses pattern recognition to sense infection and trigger an immune response against pathogen invasion. In 2006, Medzhitov and Stetson reported a novel DNA-sensing immune response independent of TLR9 which can lead to interferon regulatory factor 3 (IRF3) mediated type I interferon production (Stetson and Medzhitov, 2006). They further found that the abnormal accumulation of cytoplasmic DNA caused by the abnormality of 3′ repair exonuclease 1 (Trex1) could be sensed by unknown DNA receptors leading to fatal autoimmune symptoms (Stetson et al, 2008). The mice exhibit a systemic inflammatory phenotype, similar to familial chilblain lupus (FCL) and SLE In this model, the inactivation of TREX1 leads to abnormal accumulation of dsDNA in the cytoplasm, which leads to the overexpression of IFN-I. We summarized the current progress in developing molecular agents targeting the cGAS-STING pathway, and their therapeutic potential is discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
