Systematic profiling reveals hepatic immune and metabolic dysregulation in DNASE1L3-deficient mice.

ABSTRACT: Deoxyribonuclease 1-like 3 (DNASE1L3) is a secreted endonuclease essential for degrading extracellular DNA and maintaining immune tolerance, but its role in hepatic immune-metabolic regulation remains unclear. Using multi-omics analyses combined with immunophenotyping, we demonstrate that Dnase1l3-deficient (knockout, KO) mice exhibit disrupted myeloid differentiation, Kupffer cell M1 polarization (M1), and progressive hepatic steatosis. Integrated transcriptomic, proteomic, and metabolomic profiling revealed activation of damage-associated molecular pattern (DAMP) sensing, endoplasmic reticulum stress, redox imbalance, ferroptosis susceptibility, and lipid metabolic reprogramming. Whole-genome resequencing further identified chromosome 4 mutation hotspots linked to iron metabolism,

SUBMITTER: Lei L 

PROVIDER: S-EPMC12741396 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature