B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis.
Fiche publication
Date publication
janvier 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Pr GOTTENBERG Jacques-Eric
Tous les auteurs :
Francois A, Chatelus E, Wachsmann D, Sibilia J, Bahram S, Alsaleh G, Gottenberg JE
Lien Pubmed
Résumé
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-1beta, TGF-beta1, and CCL2 protein secretion were assessed. RESULTS: Coculture of blood B cells and dermal fibroblasts isolated from SSc patients induced IL-6, TGF-beta1, 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-beta1, and collagen secretion. B cell- and BAFF-induced collagen secretion was highly reduced by anti-TGF-beta1 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.
Référence
Arthritis Res Ther. 2013 Oct 28;15(5):R168