Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis
Open Access
- 23 March 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (5), 2451-2464
- https://doi.org/10.1172/jci131700
Abstract
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 thirty-five 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 systemic sclerosis patients. 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..Keywords
Funding Information
- NIH (U19AI110495)
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