The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder caused by mutations in genes encoding ciliary proteins. Increasing evidence suggests that immune cell infiltration, chronic inflammation, and dysregulated immune signaling pathways contribute to cyst growth, fibrosis, and progressive kidney function decline. Notably, features of chronic inflammation are already detectable in early stages of the disease, including infiltration by immune cells, elevated levels of proinflammatory cytokines, and immunologic crosstalk between immune and epithelial cells. These immune responses promote fibroblast activation and excessive extracellular matrix deposition through key signaling pathways such as NF kappa-light-chain-enhancer of activated B cells, Janus kinases-signal transducers and activators of transcription, and TGF β -small mothers against decapentaplegic, ultimately driving renal fibrosis and functional deterioration. Conversely, components of the adaptive immune system have been implicated in slowing disease progression. CD8 +T cells have been shown to exert a protective effect by limiting cyst expansion and preserving tubular architecture. Remarkably, cyst-lining epithelial cells themselves can regulate immune cell activity, highlighting a complex and dynamic interplay between ADPKD and the immune system at multiple levels. Beyond direct crosstalk, immune mechanisms may also contribute to the genotype-independent interindividual variability observed in ADPKD progression. In this review, we provide a comprehensive overview on the role of immune cells in ADPKD, offering mechanistic insight into the processes underlying cyst initiation and progression. This perspective underscores the increasing recognition that cystic kidneys share fundamental features with tumor-like microenvironments, including chronic inflammation, immune-driven matrix remodeling, and metabolic dysregulation. We further summarize emerging immune-related biomarkers and therapeutic targets, providing a foundation for future translational approaches.