Increased Granzyme K+ CD8+ T cells and senescent subset in Behçet’s disease
- 주제(키워드) Behcet's disease , immunosenescence , granzyme
- 주제(DDC) 610
- 발행기관 아주대학교 일반대학원
- 지도교수 Sun Park
- 발행년도 2025
- 학위수여년월 2025. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000034772
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Increased Granzyme K+ CD8+ T cells and senescent subset in Behçet’s disease Behçet’s disease (BD) is a complex, chronic inflammatory condition with multisystemic involvements, believed to arise from various etiologies, including immune system dysregulation. Previously we reported terminally differentiated senescent immune cells accumulate in BD and may contribute to inflammation through secreting senescence-associated secretory proteins. Recent evidence suggests the proinflammatory role of extracellular granzyme (Gzm) K, especially in aged immune cells; however, the role of GzmK in BD remains underexplored. Thus, this study focuses on GzmK-expressing CD8+ T cells and their senescent subset to elucidate their contribution to BD pathology and relationship with inflammatory cytokines. In the peripheral blood mononuclear cells (PBMC), significantly higher extracellular GzmK and GzmK+CD8+ T cells, particularly with advanced differentiation markers, were seen in active BD patients than in healthy controls. Notably, GzmK+CD8+ T cells showed a positive correlation with the expression of tumor necrosis factor alpha (TNF-α)+ lymphocytes and interferon gamma (IFN-γ)+ lymphocytes, indicating their role in promoting inflammatory responses that exacerbate BD symptoms. Additionally, the subset of GzmK+CD27-CD28- CD57+CD8+ (senescent GzmK+CD8+) T cells were positively correlated only with the TNF-α+ lymphocytes, suggesting their specific involvement in TNF-α-centered inflammatory pathways. These findings suggest that GzmK+CD8+ T cells and their senescent counterparts might not only serve as markers of active inflammation but also represent therapeutic targets for controlling inflammation in BD. Keywords: Behçet’s disease, Granzyme K, immunosenescence
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INTRODUCTION 1
MATERIAL AND METHODS 3
A. Subjects 3
B. Enzyme-linked Immunosorbent Assay for GzmA, GzmB, GzmK, and IL-6 3
C. Isolation and in vitro culture of peripheral blood mononuclear cells 3
D. Flow cytometry 4
E. Statistical analysis 4
RESULTS 8
A. Demographics and clinical characteristics 8
B. Increased GzmK serum level in active BD patients 8
C. Identification of major secreting cells for each Gzm 9
D. GzmK+CD8+ T cells were significantly higher in active BD patients' group under ex vivo condition 9
E. Increased GzmK+ senescent CD8+ T cells in the active BD patients' group and their association with clinical symptoms 9
F. Stimulation assay reveals GzmK upregulation in BD may not derive from abnormal T cell activation 10
G. Correlation between expression of TNF-α+ lymphocytes or IFN-γ+ lymphocytes and GzmK+CD8+ T cells 10
DISCUSSION 20
CONCLUSION 24
REFERENCES 25
국문요약 28
