Updated roles of cGAS-STING signaling in autoimmune diseases

Abstract

Natural immunity, the first line for the body to defense against the invasion of pathogen, serves as the body’s perception of the presence of pathogens depends on nucleic acid recognition mechanisms. The cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) signaling pathway is considered an essential pattern recognition and effector pathway in the natural immune system and is mainly responsible for recognizing DNA molecules present in the cytoplasm and activating downstream signaling pathways to generate type I interferons and some other inflammatory factors. STING, a crucial junction protein in the innate immune system, exerts an essential role in host resistance to external pathogen invasion. Also, STING, with the same character of inflammatory molecules, is inseparable from the body’s inflammatory response. In particular, when the expression of STING is upregulated or its related signaling pathways are overactivated, the body may develop serious infectious disorders due to the generation of excessive inflammatory responses, non-infectious diseases, and autoimmune diseases. In recent years, accumulating studies indicated that the abnormal activation of the natural immune cGAS-STING signaling pathway modulated by the nucleic acid receptor cGAS closely associated with the development and occurrence of autoimmune diseases (AID). Thereof, to explore an in-depth role of STING and its related signaling pathways in the diseases associated with inflammation may be helpful to provide new avenues for the treatment of these diseases in the clinic. This article reviews the activation process of the cGAS-STING signaling pathways and its related important roles, and therapeutic drugs in AID, aiming to improve our understanding of AID and achieve better diagnosis and treatment of AID.

Exacerbation of atherosclerosis by STX17 knockdown: Unravelling the role of autophagy and inflammation

“…41 Elevated or overactivated expression of STING or its related signalling pathway can lead to severe infectious diseases, non-infectious diseases and autoimmune conditions due to excessive inflammatory reactions. 42 Recent studies have provided evidence that STING mediates pro-inflammatory activation of macrophages during the occurrence and progression of AS, 43 and can induce endothelial-to-mesenchymal transition (EndMT) in ECs, accelerating endothelial dysfunction. 44 Recent evidence suggests that STING can physically interact with STX17.…”

Pathogenicity and virulence of O’nyong-nyong virus: A less studied Togaviridae with pandemic potential

“…In vitro analysis on human fibroblast cells found RIG-I is significantly upregulated post-ONNV infection, suggesting a role for the cytosolic receptors in the innate immune response against ONNV [ 133 ]. The cyclic GMP – AMP synthase stimulator of interferon genes (cGAS-STING) pathway constitutes another pivotal component of foreign DNA and cellular damage detection in the cytosol, orchestrating a robust antiviral response, but has also been implicated in various autoimmune and inflammatory disorders [ 134 ]. In vivo modelling proposes that cGAS expression is essential for mediating the innate antiviral response against various alphaviruses, including: SINV, ONNV, Venezuelan equine encephalitis virus (VEEV), and CHIKV; through a unique activation of an IRF3-driven antiviral program, independent from canonical IFN/STAT1 signalling [ 135 ].…”

cGAS-STING pathway in pathogenesis and treatment of osteoarthritis and rheumatoid arthritis

“…Addressing these challenges will be crucial for ensuring the safety and efficacy of drugs targeting the cGAS-STING pathway in diverse patient populations and disease contexts (48)(49)(50). Further research and clinical trials are needed to better understand the therapeutic potential and limitations of targeting this pathway in various diseases.…”