INPP5D/SHIP1-mediated immunometabolic remodeling of renal monocytes in idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is an antibody-mediated glomerulopathy in which podocyte-directed autoimmunity is well characterized, whereas the immunometabolic programs of innate immune cells within the renal microenvironment remain poorly defined. Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1, encoded by METHODS: Bulk and single-cell RNA-seq analyses were performed using public human IMN datasets, and the passive Heymann nephritis (PHN) rat model was used specifically for RESULTS: IMN kidneys exhibited elevated immune and stromal scores, with increased infiltration of monocytes and naïve B cells and a relative depletion of regulatory T cells. Cross-differential analyses identified five overlapping immune-metabolic genes ( CONCLUSIONS: These data delineate an INPP5D/SHIP1-centered immunometabolic program in renal monocytes as a potential regulatory factor of pathological monocyte-podocyte crosstalk in IMN. Targeting SHIP1-related PI3K/Akt pathways and monocyte immunometabolism may offer novel immunomodulatory strategies for risk stratification and disease modification in membranous nephropathy.