KIAA1199 aggravates sepsis-induced lung injury by promoting complement activation

Sepsis-induced acute lung injury (ALI) is a life-threatening condition associated with high mortality rates. While emerging evidence suggests that KIAA1199 (also known as cell migration-inducing protein, CEMIP) contributes to the pathogenesis of bacterial infections, its specific role in sepsis-induced ALI remains largely unexplored. This study aimed to investigate the role of KIAA1199 in sepsis-induced ALI. Our findings revealed that serum levels of KIAA1199 were significantly elevated in sepsis patients compared to healthy individuals, demonstrating a positive correlation with the sequential organ failure assessment (SOFA) scores. Additionally, we observed the expression of KIAA1199 increased in the lung tissue of septic mice, particularly in alveolar epithelial Type II (AT2) cells. To further elucidate its function, we generated AT2-specific KIAA1199 knockout mice and established an LPS-induced ALI model. The results indicated that KIAA1199-deficient mice exhibited improved survival rates, reduced lung injury, and decreased levels of proinflammatory cytokines. To further explore the specific downstream target of KIAA1199, RNA sequencing of AT2 cells was conducted in this study.