lncRNA-mRNA Co-expression Network Unveils Neutrophil Metabolic Reprogramming in Human Sepsis.

Sepsis is a life-threatening inflammatory syndrome driven by dysregulated immunity. Metabolic reprogramming and epigenetic regulation are now recognized as critical mechanisms underlying persistent immune cell alterations in sepsis. Neutrophils play a central role in sepsis by forming NETs, releasing inflammatory cytokines, and phagocytosing pathogens. During these processes, neutrophils undergo metabolic adaptation that supports their effector functions. Long non-coding RNAs (lncRNAs) have been implicated in multiple facets of sepsis progression, including the regulation of immune cell functions and organ injury. Recent studies further indicate that lncRNAs modulate metabolic reprogramming across various cell types during sepsis, highlighting extensive crosstalk between metabolic and epigenetic pathways. Nevertheless, the relationship between lncRNAs and metabolic reprogramming in neutrophils remains poorly understood. To better characterize the regulatory interplay between metabolic alterations and lncRNAs in neutrophils during sepsis, we performed RNA sequencing of neutrophils isolated from septic patients. We identified a set of hub differentially expressed genes enriched in amino acid metabolic processes and uncovered potential lncRNA networks that may regulate these genes. Our study delineates a broader landscape of neutrophil metabolic reprogramming in sepsis and provides a foundational co-expression network, offering new directions for investigating lncRNA-mediated amino acid metabolic alterations in neutrophils during sepsis.