B细胞激活因子中和会加重动脉样硬化
Dimitrios Tsiantoulas1,2, Andrew P Sage3, Laura Göderle1,2
1Department of Laboratory Medicine, Medical University of Vienna (D.T., L.G., M.O.-K., F.P., C.J.B.).
Circulation
|June 3, 2018
概括
在小鼠中,阻断B细胞激活因子 (BAFF) 治疗通过影响骨髓细胞而不是B细胞,意外地恶化了动脉样硬化. 这揭示了BAFF独立于B细胞的新型抗炎作用,对心血管疾病有潜在的临床影响.
科学领域:
- 免疫学
- 心血管科学
- 基因组学
背景情况:
- 动脉样性心血管疾病是全球主要的死亡原因,
- 基因组研究表明B细胞激活因子 (BAFF) 途径与冠心病有关.
- 针对自身免疫性疾病的现有抗BAFF疗法表明潜在的心血管益处,但对动脉样硬化的直接影响尚不清楚.
研究的目的:
- 研究BAFF中和对动脉样硬化的影响.
- 阐明BAFF影响动脉样硬化进展的机制.
主要方法:
- 用抗BAFF抗体治疗Apoe-/和Ldlr-/小鼠.
- 对缺乏BAFF受体,跨膜激活剂和调节剂和环素连接体相互作用剂 (TACI) 的动脉样硬化易感小鼠的分析.
- 对骨髓细胞特异性和B细胞特异性TACI删除的研究.
主要成果:
- 抗BAFF抗体治疗异常地增加了小鼠的动脉样硬化,尽管B细胞耗尽.
- 骨髓细胞特异性TACI删除,但不是B细胞特异性删除,也增加了动脉样硬化.
- 发现BAFF-TACI信号抑制了巨细胞IRF7依赖的Toll-like受体9反应和亲动脉性CXCL10的产生.
结论:
- 在动脉样硬化中,BAFF具有新的,B细胞独立的抗炎作用.
- 这些发现可能对控制心血管风险有重大临床影响.
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