ATG16L1 restrains macrophage NLRP3 activation and alveolar epithelial cell injury during septic lung injury

Myeloid-specific ATG16L1 deficiency exacerbates sepsis-induced lung injury. ATG16L1-deficient macrophages exhibit impaired LC3B lipidation and ROS accumulation, leading to NLRP3 inflammasome activation. Uncontrolled inflammatory responses in ATG16L1-deficient macrophages aggravate alveolar epithelial cell damage. Alveolar epithelial cells release dsDNA, activating the cGAS-STING-NLRP3 signaling pathway, which subsequently triggers a positive feedback activation of NLRP3. Overexpression of ATG16L1 helps mitigate lung tissue inflammation, offering a novel therapeutic direction for sepsis-induced lung injury.