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Spermidine restricts neonatal inflammation via metabolic shaping of PMN-MDSCs [RNA-seq]

GSE287178 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/04/09 Platform GPL24247
Summary
Newborns exhibit a heightened vulnerability to inflammatory disorders due to their underdeveloped immune system, yet the underlying mechanisms remain poorly understood. Here we report that plasma spermidine is correlated with the maturity of human newborns and reduced risk of inflammation. Administration of spermidine led to the remission of neonatal inflammation in mice. Mechanistic studies revealed that spermidine enhanced the generation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via downstream eIF5A hypusination (eIF5A-Hyp). Genetic deficiency or pharmacological inhibition of deoxyhypusine synthase (DHPS), a key enzyme of eIF5A-Hyp, diminished the immunosuppressive activity of PMN-MDSCs, leading to aggravated neonatal inflammation. The eIF5A-Hyp pathway was found to enhance mitochondrial function via histone acetylation-mediated epigenetic transcription of immunosuppressive signatures in PMN-MDSCs. These findings demonstrated spermidine-eIF5A-Hyp metabolic axis as a master switch to restrict neonatal inflammation.
Published in
Spermidine restricts neonatal inflammation via metabolic shaping of polymorphonuclear myeloid-derived suppressor cells
Chen J, Zhu L, Cui Z et al. · The Journal of clinical investigation 2025 · PMID 40166929 · doi:10.1172/JCI183559
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Also filed as BioProject PRJNA1187882 and SRA study SRP547690. Searching any of these in the dataset finder brings you back here.

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