期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 130, 期 5, 页码 2451-2464出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI131700
关键词
-
资金
- NIH Autoimmune Centers of Excellence [U19 AI 110495, UM1 AI110498]
- Rheumatology Research Foundation Scientist Development Award
- Union Chimique Belge (UCB)
- JSPS [JP18KK0260]
- Takeda Science Foundation
- Work Visit Grant of the Amsterdam Infection and Immunity Institute
- NIH [AI113163]
- NIAID [P30AI060354]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P30-AR06958]
Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4(+) cytotoxic T cells and CD8(+) T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR-expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4(+) T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据