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.
Hong-Ling Jia, Hang Zhao, Yan Li et al.· Clinical and Experimental Me...· 0 citations
Microglia are central regulators of the cellular phase of Alzheimer's disease (AD). Under chronic exposure to amyloid-β, pathological tau, and aging-associated bioenergetic decline, these cells undergo immunometabolic remodeling that may initially be adaptive. As stress persists, this remodeling can become maladaptive, marked by disordered glycolysis, disturbed lipid handling, mitochondrial dysfunction, and compensatory failure. In this review, we organize these changes as a stage-dependent trajectory from adaptive remodeling to functional decompensation. We introduce the "metabolic paradox" as an operational descriptor: a concurrent, same-cell mismatch between increased substrate uptake or inflammatory activation and declining bioenergetic efficiency and homeostatic function. Along this trajectory we examine neurovascular energy bottlenecks, substrate redistribution, triggering receptor expressed on myeloid cells 2 (TREM2)/apolipoprotein E (APOE)-dependent lipid homeostasis, mitochondrial and proteostatic collapse, and their links to persistent neuroinflammation, defective phagocytosis, aberrant synaptic pruning, and senescence-like dysfunction. We synthesize prior primary findings and stratify each major claim by evidentiary strength, avoiding the overinterpretation of model-specific results as patient-level mechanisms. Finally, we frame immunoprevention as mechanism-based, early-stage metabolic intervention to preserve homeostatic microglial function, a strategy whose clinical benefit remains a hypothesis requiring prospective testing.
Yue Zou, Yi Ou, Hang Zhao et al.· Biomedicine & pharmacotherap...· 0 citations
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