B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis

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.
Type de document :
Article dans une revue
Arthritis Research & Therapy, BioMed Central, 2013, 15 (5), pp.R168
Liste complète des métadonnées

Littérature citée [35 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00906489
Contributeur : Ed. Bmc <>
Soumis le : mardi 19 novembre 2013 - 21:08:01
Dernière modification le : mercredi 14 mars 2018 - 16:43:43
Document(s) archivé(s) le : jeudi 20 février 2014 - 09:45:54

Fichiers

ar4352.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

  • HAL Id : inserm-00906489, version 1

Collections

Citation

Antoine François, Emmanuel Chatelus, Dominique Wachsmann, Jean Sibilia, Seiamak Bahram, et al.. B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis. Arthritis Research & Therapy, BioMed Central, 2013, 15 (5), pp.R168. 〈inserm-00906489〉

Partager

Métriques

Consultations de la notice

180

Téléchargements de fichiers

132