Immunomodulation by MSCs in Kidney Diseases: Molecular Mechanisms

Background: Kidney disease progression is driven by immune dysregulation, inflammation, and fibrosis. Mesenchymal stem cells (MSCs) act via paracrine signaling (exosomes, IDO, PGE2, TGF-β) to modulate immunity.Methods: PubMed and Web of Science (2000-2026) were searched using keywords related to MSCs, kidney diseases, and the signaling pathways. Results: This review dissects molecular mechanisms by which MSCs regulate innate and adaptive immunity in kidney diseases. Focus is placed on specific intracellular cascades (NF-κB, NLRP3, PI3K-Akt, STAT, TGF-β/Smad, Wnt/β-catenin, cAMP-PKA, AhR, Nrf2, SIRT1·PGC-1α) and cell‑type responses (macrophages, tubular epithelial cells, podocytes, endothelial cells). Unlike broader reviews, we systematically explore cross-talk and compensatory interactions among pathways, and their shifting dominance from acute inflammation to chronic fibrosis.Conclusions: Critical gaps are identified: validation using conditional knockout models, exosome uptake routes, and rational MSC engineering. By integrating molecular‑resolution mechanisms, this review provides a foundation for pathway‑targeted, biomarker-guided MSC‑based therapies for kidney diseases.