CD177 promotes NLR inflammasome activation in acute respiratory distress syndrome by remodeling neutrophil glycolytic metabolism.

Acute respiratory distress syndrome is a high-mortality lung disorder driven by excessive neutrophil activation. While neutrophils are central to acute respiratory distress syndrome, the metabolic pathways fueling their inflammatory response remain unclear. This study identifies CD177 as a critical regulator of neutrophil glycolysis and NLRP3 inflammasome activation. Bioinformatics and animal models show that elevated CD177 correlates strongly with increased lactate and interleukin-1β levels. In vitro experiments demonstrate that CD177 knockdown reduces glycolytic flux and suppresses interleukin-1β release, a process reversed by lactate supplementation. Furthermore, treating acute respiratory distress syndrome mice with anti-CD177 antibodies significantly reduces pulmonary edema and tissue injury. These results establish the CD177-glycolysis-NLRP3 axis as a major driver of lung inflammation. Targeting this metabolic checkpoint provides a promising strategy for treating acute respiratory distress syndrome.