PFKFB3 promotes sepsis-induced acute lung injury by enhancing NET formation by CXCR4hi neutrophils

CXCR4hi neutrophils, which are a subset of neutrophils with high CXCR4 expression, are important contributors to sepsis-induced acute lung injury (ALI). PFKFB3, a key glycolysis gene, plays an essential role in neutrophil inflammatory activation. However, the specific involvement of PFKFB3 in sepsis-induced ALI remains unclear. Here, we observed that PFKFB3 was upregulated in CXCR4hi neutrophils and facilitated sepsis-induced ALI. Mechanistically, we observed that PFKFB3 promoted sepsis-induced ALI by enhancing neutrophil extracellular trap (NET) formation by CXCR4hi neutrophils. Further study indicated that PFKFB3 promoted NET formation by upregulating glycolytic metabolism in CXCR4hi neutrophils. In summary, our study uncovered a new mechanism by which CXCR4hi neutrophils trigger sepsis-induced ALI by promoting NET formation, which is supported by PFKFB3-mediated glycolytic metabolism.