DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis - PubMed
3 days ago
- #immunometabolism
- #macrophages
- #sepsis
- DPEP2 is identified as an immunotherapeutic target in sepsis through analysis of single-cell and bulk RNA sequencing data.
- Reduced DPEP2 expression in monocytes/macrophages of septic patients correlates with worse inflammation severity and clinical outcomes.
- DPEP2 knockdown in macrophages increases inflammation, while its loss in septic mice decreases survival by exacerbating inflammation and organ damage.
- Sepsis-induced EGR1 represses DPEP2 transcription, reducing enzymatic cleavage of leukotriene D4 (LTD4), leading to metabolic flux redirection towards prostaglandin E2 overproduction.
- Lipid nanoparticle (LNP)-mediated delivery of DPEP2 mRNA to monocytes/macrophages reduces inflammation and organ damage in septic mice, suggesting a potential therapy.