Fig. 5

cGAS-STING Pathway Antagonists in the Setting of lung diseases. Multiple classes of cGAS-STING antagonists have shown benefit against lung diseases models. (1).Activation of cGAS-STING is implicated in the pathogenesis of sepsis-associated acute lung injury (ALl), mediated by dysregulated alveolar macrophages. (2). CD11b + macrophages inhibit STING signaling, suppressing inflammation in ALI. Loss triggers inflammatory macrophage expansion, neutrophil accumulation, and vascularbarrier dysfunction. (3). STING participates in ALI development via cytosolic DNA-STING-NLRP3 axis, with LPS-induced mitochondrial DNA release activating STING and NLRP3 infammasome. (4). NAT10 downregulation promotes ULK1-STING-NLRP3 axis, facilitating pyroptosis in neutrophils, contributing to ALI progression. (5). NLRC3 negatively regulates STING, its overexpression decreases lung inflammation in LPS-treated mice. (6). HDAC3 mediates macrophage pyroptosis by activating cGAS-STING, suggesting a potential therapeutic target for ALI. (7). SIRT1 deficiency aggravates ALI due to mitophagy defects and NLRP3/STING hyperactivation, highlighting its role in regulating mitochondrial sianals. (8). Circulating mtDNA-mediated STING activation obstructs autophagic flux, exacerbating ALI in sepsis patients. (9). NETs induce endothelial cell damage via STING activation, magnifying dysregulated coagulation and inflammation in sepsis-associated All. (10). Inhibition of STING or disruption of NETs improves prognosis by reducing inflammation and coagulation, suggesting a potential therapeutic strategy for ALI