B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis.
B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis.
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DOI：
10.1186/ar4352
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发表时间：
2013-10-28
影响因子：
4.9
通讯作者：
Gottenberg JE
中科院分区：
文献类型：
--
作者：
François A;Chatelus E;Wachsmann D;Sibilia J;Bahram S;Alsaleh G;Gottenberg JE
B淋巴细胞可能在系统性硬化症（SSc）皮肤纤维化中起致病作用。B细胞活化因子（BAFF）是B细胞活化的关键细胞因子，在SSc患者的血清和皮肤中增加。然而，B细胞直接刺激真皮成纤维细胞的能力和BAFF的作用尚未完全了解。因此，我们研究了B细胞和BAFF参与真皮成纤维细胞表达胶原蛋白和促纤维化标志物。进行来自健康献血者的血液B细胞和用抗IgM和BAFF刺激的正常或SSc真皮成纤维细胞的共培养。通过定量RT-PCR测定α-SMA、TIMP 1、MMP 9、COL 1A 1、COL 1A 2和COL 3A 1 mRNA表达。评估可溶性胶原、BAFF、IL-6、IL-1β、TGF-β1和CCL 2蛋白分泌。从SSc患者分离的血液B细胞和真皮成纤维细胞的共培养诱导IL-6、TGF-β1、CCL 2和胶原分泌，以及真皮成纤维细胞中的α-SMA、TIMP 1和MMP 9表达。Transwell分析表明，这种诱导依赖于细胞-细胞接触。向共培养物中加入抗IgM和BAFF可增加IL-6、CCL 2、TGF-β1和胶原分泌。抗TGF-β1抗体可显著降低B细胞和BAFF诱导的胶原分泌。我们的研究结果首次显示了B细胞对真皮成纤维细胞产生胶原蛋白的直接作用，BAFF进一步增强了这种作用。因此，这些结果证明了B细胞和BAFF在纤维化和系统性硬化症中的新的致病作用。
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. 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. 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. 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.
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影响因子：
--
作者：
Komura, Kazubiro;Yanaba, Koichi;Sato, Shinichi
通讯作者：
Sato, Shinichi
影响因子：
4.4
作者：
Sato, S;Hasegawa, M;Takehara, K
通讯作者：
Takehara, K
影响因子：
6
作者：
Hasegawa, Minoru;Hamaguchi, Yasuhito;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
影响因子：
3.7
作者：
Couture, Patrick;Paradis-Massie, Jeremie;Thibault, Gaetan
通讯作者：
Thibault, Gaetan
影响因子：
5.5
作者：
Abraham, D. J.;Krieg, T.;Distler, O.
通讯作者：
Distler, O.