Abstract
BACKGROUND: Sepsis-induced immunosuppression involves complex molecular mechanisms, including dysregulated long noncoding RNAs (lncRNAs), which remain poorly understood. OBJECTIVE: We aimed to identify immunosuppression-related lncRNAs and their functional pathways in sepsis. Methods: Using weighted gene coexpression network analysis (WGCNA), we analyzed lncRNA profiles from peripheral blood mononuclear cells (PBMCs) of three sepsis patients and three healthy controls. Key modules linked to immunosuppression were validated via RT-PCR and external datasets. Pathway enrichment and protein interaction networks were employed to prioritize mechanisms. RESULTS: A sepsis-associated module containing 4,193 lncRNAs revealed three immunosuppression-related pathways: Th17 cell differentiation, cytokine-cytokine receptor interactions, and cancer-related proteoglycan signaling. Protein-protein interaction networks identified three central genes (SLFN12, ICOS, IKZF2) and their linked lncRNAs (ENSG00000267074, lnc-ICOSLG-1, lnc-IKZF2-7), all significantly downregulated in sepsis patients. CONCLUSION: Our findings highlight novel lncRNA-regulated pathways in sepsis-induced immunosuppression, providing potential targets for improved diagnosis and therapy.