Nucleic Acid Diversity in cGAS-STING Pathway Activation and Immune Dysregulation

The cGAS-STING pathway initiates the core cascade of innate immune defense by recognizing pathogen-associated and self-derived abnormal nucleic acids, and key molecules (such as cGAS, STING, downstream IFN-β, IL-6, etc.) may serve as biomarkers in various diseases. The diverse mechanisms by which distinct nucleic acids activate this pathway provide novel insights for therapeutic strategies targeting infectious diseases, cancer, and autoimmune disorders. To prevent aberrant cGAS-STING pathway activation, cells employ multiple regulatory mechanisms, including restricting self-DNA recognition and terminating downstream signaling. Strategies to mitigate pathological activation involve reducing nucleic acid accumulation through nuclease degradation (e.g., of mitochondrial DNA or neutrophil extracellular traps, NETs) or directly inhibiting cGAS or STING. This review elucidates the molecular mechanism of nucleic acid-mediated regulation of cGAS-STING and its role in disease regulation.