Etanercept attenuates collagen-induced arthritis by modulating the association between BAFFR expression and the production of splenic memory B cells
Etanercept attenuates collagen-induced arthritis by modulating the association between BAFFR expression and the production of splenic memory B cells
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依那西普通过调节 BAFFR 表达与脾记忆 B 细胞生成之间的关联来减轻胶原诱导的关节炎。
DOI：
10.1016/j.phrs.2012.11.003
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发表时间：
2013-02-01
影响因子：
9.3
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Wang, Qing-tong;Wu, Yu-jing;Wei, Wei
抗肿瘤坏死因子-α药物被批准用于治疗类风湿性关节炎(RA)。许多研究已经调查了这些药物对T细胞反应的影响；然而，一些线索表明，它也可能针对B细胞。本研究旨在探讨可溶性肿瘤坏死因子-α受体依那西普对II型胶原诱导的关节炎(CIA)B细胞功能及其向记忆性B细胞发育的影响及其机制。从CII免疫后第24天开始，每隔2-3天对小鼠进行评估，以确定两项临床参数：关节炎总体评估和关节肿胀计数(SJC)。检测小鼠血清中IgG1、IgG2a和抗CII抗体浓度，观察脾组织病理改变和B细胞增殖情况。用流式细胞仪检测小鼠脾组织中总记忆B细胞的百分率。免疫组织化学方法检测BAFFR。在CIA小鼠中，依那西普显著抑制关节炎总体评分和SJC，减少抗CII、IgG1和IgG2a抗体的产生，并不同程度地预防脾组织病理改变，但对脾B细胞增殖无明显影响。依那西普还能降低小鼠脾组织中CD27(+)记忆B细胞的百分率。依那西普治疗后BAFFR表达进一步增加，CD27表达显著降低，BAFFR水平与记忆B细胞百分比呈负相关。我们的研究结果表明，BAFFR表达增加对B细胞的激活和记忆B细胞的生成具有调节作用，这可能是依那西普治疗作用的机制之一。(C)2012爱思唯尔有限公司。保留所有权利。
Anti-tumour necrosis factor-alpha (TNF-alpha) drugs are approved for the treatment of rheumatoid arthritis (RA). Many studies have investigated the effect of these drugs on the T cell response; however, some clues have indicated that it may also target B cells. This study was carried out to explore the potential effects and mechanisms of etanercept, a soluble TNF-alpha receptor, on the function of B cells and their development into memory B cells in type II collagen (CII)-induced arthritis (CIA). Beginning on day 24 after CII immunisation, the mice were evaluated every 2-3 days to determine two clinical parameters: their arthritis global assessment and swollen joint count (SJC). The serum concentrations of IgGl, IgG2a and anti-CII antibodies and the splenic pathology and proliferation of B cells were measured. The percentage of total memory B cells in the spleen was analysed with flow cytometry. BAFFR was detected by immunohistochemistry. In CIA mice, etanercept markedly suppressed the arthritis global assessment and the SJC, reduced the production of anti-CII, IgG1 and IgG2a antibodies, and prevented spleen histopathology to varying degrees; however, it had no obvious effect on splenic B cell proliferation. Etanercept also decreased the percentage of total CD27(+) memory B cells in the spleen. Treatment with etanercept was associated with a further increase in BAFFR expression, a significant reduction in CD27 expression, and a negative correlation between the levels of BAFFR and the percentage of memory B cells. Our findings showed that increased BAFFR expression has a regulatory effect on the activation of B cells and the generation of memory B cells, which may be one of the mechanisms of the therapeutic effects of etanercept. (C) 2012 Elsevier Ltd. All rights reserved.