[Research progress on the correlation and treatment of the cGAS-STING pathway in systemic lupus erythematosus]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, characterized by inflammation and immune-mediated damage to multiple organ systems. Emerging evidence demonstrates that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays a pivotal role in the pathogenesis of SLE. The cGAS-STING pathway is a pattern recognition pathway of the innate immune system. After cGAS senses double-stranded DNA or endogenous DNA in the cytoplasm, it generates 2'3'-cyclic GMP-AMP to mediate intracellular signal transduction. This process activates STING, which in turn promotes the production of downstream interferons and other immune factors, ultimately triggering infection responses, cellular stress, and tissue damage. Under physiological conditions, the cGAS-STING pathway exerts protective functions in host defense. However, factors such as persistent activation may lead to dysregulation of the pathway, resulting in autoimmune diseases. Recent studies have explored interventions targeting this pathway at multiple levels, including genes, mitochondrial membranes, exonucleases, and lipopolysaccharides(LPS), which result in varying degrees of inhibition. These approaches offer novel therapeutic strategies for SLE. This study comprehensively reviews the recent research progress on inhibiting SLE-related inflammatory factor production via the cGAS-STING signaling axis by dividing the cGAS-STING pathway into two stages: dsDNA sensing and intracellular signal transduction. It also summarizes the existing therapeutic approaches related to this pathway, providing insights for more effective treatment of SLE.