J Leukoc Biol. 2026 Apr 21:qiag051. doi: 10.1093/jleuko/qiag051. Online ahead of print.
ABSTRACT
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.
PMID:42047316 | DOI:10.1093/jleuko/qiag051