TY - JOUR
T1 - Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis
AU - Maehara, Takashi
AU - Kaneko, Naoki
AU - Perugino, Cory A.
AU - Mattoo, Hamid
AU - Kers, Jesper
AU - Allard-Chamard, Hugues
AU - Mahajan, Vinay S.
AU - Liu, Hang
AU - Murphy, Samuel J.H.
AU - Ghebremichael, Musie
AU - Fox, David
AU - Payne, Aimee S.
AU - Lafyatis, Robert
AU - Stone, John H.
AU - Khanna, Dinesh
AU - Pillai, Shiv
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85081675325&partnerID=8YFLogxK
U2 - https://doi.org/10.1172/JCI131700
DO - https://doi.org/10.1172/JCI131700
M3 - Article
C2 - 31990684
SN - 0021-9738
VL - 130
SP - 2451
EP - 2464
JO - Journal of clinical investigation
JF - Journal of clinical investigation
IS - 5
ER -