4.8 Article

Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis

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

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资金

  1. NIH Autoimmune Centers of Excellence [U19 AI 110495, UM1 AI110498]
  2. Rheumatology Research Foundation Scientist Development Award
  3. Union Chimique Belge (UCB)
  4. JSPS [JP18KK0260]
  5. Takeda Science Foundation
  6. Work Visit Grant of the Amsterdam Infection and Immunity Institute
  7. NIH [AI113163]
  8. NIAID [P30AI060354]
  9. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P30-AR06958]

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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.

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