期刊
ARTHRITIS AND RHEUMATISM
卷 60, 期 4, 页码 1119-1128出版社
WILEY
DOI: 10.1002/art.24432
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资金
- University of Pittsburgh School of Medicine
- Scleroderma Research Fund (University of Pittsburgh Division of Rheumatology and Clinical Immunology)
- Taub Fund (Chicago, IL)
- Zale Foundation (Dallas, TX)
- Shoemaker Fund (Arthritis Foundation, Western Pennsylvania Chapter)
- Scleroderma Foundation
Objective. T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell-derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc. Methods. To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (IcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation. Results. High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in IcSSc patients. Conclusion. Dysregulated IL-13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target.
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