Longevity & AgingRestoring a Lost Enzyme in Immune Cells Calms Runaway Inflammation in Septic Mice
Sepsis kills partly through runaway inflammation, and treatments that safely restrain it are lacking. Using single-cell and bulk RNA sequencing of patient blood, researchers found that the lipid-metabolizing enzyme DPEP2 is sharply reduced in circulating monocytes during early sepsis. Lower DPEP2 tracked with higher inflammation and illness severity scores. In mice and cell models, losing DPEP2 in macrophages worsened inflammation, organ damage, and survival. The mechanism: sepsis induces the transcription factor EGR1, which represses DPEP2. That blocks breakdown of leukotriene D4, pushing metabolism toward excess prostaglandin E2 and stronger NF-κB signaling. Lipid nanoparticles delivering Dpep2 mRNA to monocytes/macrophages reduced inflammation and organ injury in septic mice. This is preclinical work, but it points to DPEP2 as both a biomarker and a therapeutic target.
