GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327100/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327100GEOGSEfalseMesenchymal stem cell–derived extracellular vesicles alleviate immunoparalysis in sepsis-associated ARDS via reprogramming the lactate–H3K18 lactylation–PSMD14 axisSepsis-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.2026/04/07GSE327100GSM9648282GSM9648283GSM9648284GSM9648285GSM9648286GSM9648287GSM9648288GSM96482891679124676327100Homo sapiens