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天生的反应激活器B细胞通过刺激T助手-1适应性免疫来加剧动脉样硬化
Ingo Hilgendorf1, Igor Theurl, Louisa M S Gerhardt
1Center for Systems Biology, Massachusetts General Hospital, Boston (I.H., I.T., L.M.S.G., C.S.R., G.F.W., Y.I., C.W., H.Y.L., M.N., R.W., F.K.S.); Department of Internal Medicine VI, Infectious Diseases, Immunology Rheumatology, Pneumology, University Hospital of Innsbruck, Innsbruck, Austria (I.T.); Toronto General Research Institute, University Health Network, Toronto, ON, Canada (C.S.R., N.D.); Department of Medicine, University of California, San Diego, La Jolla (A.G., J.L.W.); Department of Gastroenterology, Hepatology and Infectious Diseases, University of Duesseldorf, Duesseldorf, Germany (T.A.W.H.); Department of Cardiology and Angiology I, University Heart Center Freiburg, Freiburg, Germany (C.W., A.Z.); Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA (G.K.S., P.L.); Department of Pathology (J.B.) and Division of Vascular Surgery (B.B.R.), Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, ON, Canada; and Department of Systems Biology, Harvard Medical School, Boston, MA (R.W.).
天生的反应激活器 (IRA) B细胞通过驱动T辅助-1细胞反应促进动脉样硬化. 这些B细胞,产生粒细胞巨细胞殖民地刺激因子,恶化了小鼠和人类的疾病进展.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
背景情况:
- 动脉样硬化涉及白细胞和氧化脂蛋白的积累.
- 白细胞衍生媒介调节动脉样硬化病变的发展.
- 天生的反应激活器 (IRA) B细胞是一种新型细胞类型,在动脉样硬化中发挥的作用尚不清楚.
研究的目的:
- 为了研究IRA B细胞在动脉样硬化中的功能.
- 确定IRA B细胞影响动脉样硬化的免疫反应的机制.
主要方法:
- 在小鼠和人类动脉样硬化模型中分析IRA B细胞种群.
- 使用缺乏B细胞衍生粒细胞巨细胞殖民地刺激因子的混合奇米鼠.
- 评估免疫细胞种群,树突细胞扩张和T辅助细胞分化.
主要成果:
- 在动脉样硬化期间,IRA B细胞通过依赖Myd88的信号传递在二次淋巴体器官中增加.
- 缺少B细胞衍生型粒细胞巨细胞殖民地刺激因子的小鼠表现出较小的病变,巨细胞和T细胞减少.
- IRA B 细胞促进经典的树突细胞扩张,导致 T 辅助-1 细胞生成和 IgG1-to-IgG2c 开关.
结论:
- 颗粒细胞巨细胞殖民地刺激因子产生IRA B细胞加剧动脉样硬化.
- 伊拉B细胞促进T助手-1相关的免疫环境,恶化了动脉样硬化中的白细胞反应.
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