CD177 Promotes NLR Inflammasome Activation in Acute Respiratory Distress Syndrome by Remodeling Neutrophil Glycolytic Metabolism

Acute respiratory distress syndrome (ARDS) is a high-mortality lung disorder driven by excessive neutrophil activation. While neutrophils are central to ARDS, 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 IL-1β levels. In vitro experiments demonstrate that CD177 knockdown reduces glycolytic flux and suppresses IL-1β release, a process reversed by lactate supplementation. Furthermore, treating ARDS 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 ARDS.