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Mesenchymal stem cell–derived extracellular vesicles alleviate immunoparalysis in sepsis-associated ARDS via reprogramming the lactate–H3K18 lactylation–PSMD14 axis

GSE327100 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 8 samples Submitted 2026/04/07 Platform GPL16791Platform GPL24676
Summary
Sepsis-associated acute respiratory distress syndrome (S-ARDS) is characterized by immune dysfunction and high mortality. Here, we show that elevated lactate induces P300-dependent H3K18 lactylation, which enhances PSMD14 transcription. Increased PSMD14 activates the AKT/mTOR pathway, leading to macrophage immunosuppression, including reduced inflammatory cytokine production, impaired phagocytosis, increased M2 polarization, and T cell dysfunction.Integrated analyses of public datasets, RNA-seq, and ChIP-seq identified PSMD14 as a key immune-related gene associated with poor outcomes and reduced HLA-DR expression in patients. Extracellular vesicles derived from P300 inhibitor (C646)-preconditioned mesenchymal stem cells suppress the H3K18la–PSMD14 axis, restore immune function, and improve survival.
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Also filed as BioProject PRJNA1449442 and SRA study SRP689593. Searching any of these in the dataset finder brings you back here.

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