Single-cell transcriptomic landscape delineates pathogenic NK cell subpopulations and key mediators in systemic inflammatory response syndrome
TL;DR
Findings delineate dynamic NK subpopulation remodeling during SIRS and validate IGF1/IGF1R as a potential key pathway governing NK effector function, providing a transcriptomic basis for identifying candidate biomarkers and potential therapeutic targets in SIRS.
Abstract
Systemic inflammatory response syndrome (SIRS) carries high ICU morbidity, sepsis lacks standardized therapies, and stage-variable natural killer (NK) cell function in SIRS remains poorly defined due to insufficient single-cell evidence. Herein, we analyzed public LPS-induced SIRS peripheral blood single-cell RNA sequencing (scRNA-seq) data (GSE212092) via multiple bioinformatic algorithms to dissect NK heterogeneity, followed by in vitro functional verification using NK-92 cells with IGF1 stimulation or IGF1R knockdown. We identified distinct cell types and 6 distinct NK subpopulations (C0-C5). Pro-inflammatory C0 and proliferative C2 IGF1R⁺ expanded in early SIRS, whereas stemness-high C3-C5 accumulated during late immunosuppression. MHC-I and CCL5-CCR1 dominated NK-related intercellular crosstalk, and unique transcription regulatory modules existed across NK subpopulations. Functional assays verified IGF1/IGF1R signaling dose-dependently promotes NK inflammatory cytokine release, cytotoxic gene expression, cell viability and target cell killing. These findings delineate dynamic NK subpopulation remodeling during SIRS and validate IGF1/IGF1R as a potential key pathway governing NK effector function, providing a transcriptomic basis for identifying candidate biomarkers and potential therapeutic targets in SIRS.