Stromal cell-derived itaconate promotes endometriosis via macrophage NRF2 and lysosomal pH modulation - PubMed
8 hours ago
- #Macrophage
- #Endometriosis
- #Itaconate
- Endometriosis (EM) is linked to immune dysregulation and macrophage dysfunction.
- Excessive itaconate accumulation in EM lesions is due to elevated ACOD1 expression in ectopic stromal cells (ESCs).
- ESC-derived itaconate is internalized by peritoneal macrophages, suppressing pro-inflammatory activity and phagocytosis.
- Itaconate activates NRF2 signaling in macrophages, repressing pro-inflammatory genes.
- Itaconate enhances lysosomal acidification, reducing calcium release and inhibiting p38-MAPK activation.
- Inhibition of ACOD1 in vivo restored macrophage function and reduced lesion burden.
- Exogenous 4-octyl itaconate worsened disease progression.
- The study identifies an 'ESC-ACOD1-itaconate-macrophage' axis in EM immunosuppression.