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.