• Identified the TRAF3-ULK1-NLRP3 regulatory axis as a critical pathway driving alveolar macrophage pyroptosis in acute lung injury (ALI).
• Demonstrated that ULK1 suppresses NLRP3 expression, reducing macrophage pyroptosis and mitigating ALI, while TRAF3 ubiquitinates ULK1 to enhance NLRP3 activation and exacerbate ALI.
• Confirmed findings through integrated bioinformatics, in vitro, and in vivo experiments, revealing abundant M0 and M1 alveolar macrophages in ALI tissues.
• Proposed targeting the TRAF3-ULK1-NLRP3 axis as a promising therapeutic strategy for ALI treatment.