Immune hyperactivity in hemodialysis patients is associated with interferon gamma-induced trained immunity.

Hemodialysis patients experience persistent inflammation marked by pro-inflammatory monocytes. We hypothesized that the hyper-responsiveness of innate immune cells in these patients is facilitated by trained immunity, a form of innate immune memory. Hemodialysis patients displayed elevated monocyte counts, and isolated peripheral blood mononuclear cells showed significantly heightened cytokine responses after Toll-like receptor stimulation, both indicative of trained immunity. Importantly, plasma interferon gamma (IFN-γ) concentrations positively correlated with cytokine responses. Whole-genome RNA-sequencing revealed enrichment of interferon response pathways, particularly in patients whose monocytes exhibited the most pronounced cytokine production upon restimulation. experiments confirmed that trained immunity induction depends on IFN-γ, produced by CD4 T cells. Our findings demonstrate that hemodialysis patients display a dysregulated immune response characterized by trained immunity and that this might be mediated by IFN-γ. These insights suggest that targeting IFN-γ could be a promising strategy to mitigate damaging immune hyperactivity in dialysis patients.

© 2026 The Authors.

PMID: 42389578