Increased Granzyme K+CD8+T cells and senescent subset in Beh?et's disease

Abstract

Objectives: Beh & ccedil;et's disease (BD) is a chronic inflammatory condition with immune system dysregulation. Recent evidence suggests proinflammatory roles of extracellular granzyme K (GzmK), particularly in aged immune cells. This study investigated GzmK-expressing CD8+ T cells and their senescent subset in BD pathology. Methods: We analysed lymphocyte subsets in blood samples from 19 active BD (aBD), 19 inactive BD (iaBD), and 19 healthy controls (HC) using flow cytometry and granzymes, as well as IL-6 using enzyme-linked immunosorbent assay. Results: Active BD patients showed significantly higher serum GzmK levels and GzmK+CD8+ T cells with advanced differentiation markers. GzmK+CD8+ T cells positively correlated with TNF-alpha+ and IFN-gamma+ lymphocytes. The senescent subset (GzmK+CD27-CD28-CD57+CD8+) specifically correlated with TNF-alpha+ lymphocytes, indicating involvement in TNF-alpha-centered inflammatory pathways. Conclusion: GzmK+CD8+ T cells and their senescent counterparts are not merely biomarkers of disease activity but may function as extracellular proinflammatory effectors that amplify the TNF-alpha-mediated inflammatory loop in BD. Targeting the GzmK-senescence axis represents a promising therapeutic strategy for managing chronic inflammation in BD.