INPP5D/SHIP1-mediated immunometabolic remodeling of renal monocytes in idiopathic membranous nephropathy - PubMed
3 hours ago
- #immunometabolism
- #monocytes
- #nephropathy
- INPP5D/SHIP1-mediated immunometabolic remodeling in renal monocytes is linked to idiopathic membranous nephropathy (IMN).
- IMN is an antibody-mediated glomerulopathy with poorly defined immunometabolic programs in innate immune cells.
- SHIP1, encoded by INPP5D, is a negative regulator of PI3K signaling in myeloid cells and a potential immunopharmacologic target.
- Bulk and single-cell RNA-seq analyses identified INPP5D as significantly upregulated in monocytes in IMN.
- IMN kidneys showed elevated immune and stromal scores, increased monocyte and naïve B cell infiltration, and reduced regulatory T cells.
- Single-cell analyses revealed renal monocytes in IMN have enhanced steroid biosynthesis and skewed differentiation toward an M1-like state.
- The passive Heymann nephritis (PHN) rat model validated key features of IMN, including upregulated SHIP1 and PI3K/Akt signaling.
- Targeting SHIP1-related pathways may offer new immunomodulatory strategies for IMN risk stratification and treatment.