1. B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis.
- Author
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François A, Chatelus E, Wachsmann D, Sibilia J, Bahram S, Alsaleh G, and Gottenberg JE
- Subjects
- Actins genetics, Actins immunology, Actins metabolism, Antibodies, Anti-Idiotypic immunology, Antibodies, Anti-Idiotypic pharmacology, B-Cell Activating Factor metabolism, B-Cell Activating Factor pharmacology, B-Lymphocytes cytology, B-Lymphocytes metabolism, Cells, Cultured, Chemokine CCL2 immunology, Chemokine CCL2 metabolism, Coculture Techniques, Collagen genetics, Collagen metabolism, Enzyme-Linked Immunosorbent Assay, Fibroblasts metabolism, Fibroblasts pathology, Fibrosis genetics, Fibrosis immunology, Fibrosis metabolism, Gene Expression drug effects, Gene Expression immunology, Humans, Immunoglobulin M immunology, Interleukin-6 immunology, Interleukin-6 metabolism, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 immunology, Muscle, Smooth chemistry, Reverse Transcriptase Polymerase Chain Reaction, Scleroderma, Systemic genetics, Scleroderma, Systemic immunology, Scleroderma, Systemic metabolism, Skin immunology, Skin metabolism, Skin pathology, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-1 immunology, Transforming Growth Factor beta1 immunology, Transforming Growth Factor beta1 metabolism, B-Cell Activating Factor immunology, B-Lymphocytes immunology, Collagen immunology, Fibroblasts immunology
- Abstract
Introduction: B lymphocytes might play a pathogenic role in dermal fibrosis in systemic sclerosis (SSc). B-cell activating factor (BAFF), a key cytokine for B-cell activation, is increased in the serum and the skin of patients with SSc. However, the ability of B cells directly to stimulate dermal fibroblasts and the role of BAFF are not fully understood. We therefore investigated the involvement of B cells and BAFF in the expression of collagen and profibrotic markers by dermal fibroblasts., Methods: Cocultures of blood B cells from healthy blood donors and normal or SSc dermal fibroblasts stimulated with anti-IgM and BAFF were performed. Alpha-SMA, TIMP1, MMP9, COL1A1, COL1A2, and COL3A1 mRNA expression were determined by quantitative RT-PCR. Soluble collagen, BAFF, IL-6, IL-1β, TGF-β1, and CCL2 protein secretion were assessed., Results: Coculture of blood B cells and dermal fibroblasts isolated from SSc patients induced IL-6, TGF-β1, CCL2, and collagen secretion, as well as Alpha-SMA, TIMP1, and MMP9 expression in dermal fibroblasts. Transwell assays demonstrated that this induction was dependent on cell-cell contact. Addition of anti-IgM and BAFF to the coculture increased IL-6, CCL2, TGF-β1, and collagen secretion. B cell- and BAFF-induced collagen secretion was highly reduced by anti-TGF-β1 antibodies., Conclusions: Our results showed for the first time a direct role of B cells on the production of collagen by dermal fibroblasts, which is further enhanced by BAFF. Thus, these results demonstrate a new pathogenic role of B cells and BAFF in fibrosis and systemic sclerosis.
- Published
- 2013
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