常规树突细胞在免疫和胆固醇之间的十字路口在动脉样硬化中的恒常状态
Emmanuel L Gautier1, Thierry Huby, Flora Saint-Charles
1INSERM UMR-S U939, Hôpital de la Pitié, Paris, France.
Circulation
|April 22, 2009
概括
树突细胞 (DCs) 通过影响免疫反应和胆固醇水平,在动脉样硬化中发挥关键作用. 提高DC寿命出乎意料地降低了胆固醇,这表明DC在这种复杂的疾病中起着保护作用.
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
- 动脉样硬化病原体的产生
背景情况:
- 免疫炎症机制是动脉样硬化的主要原因.
- 免疫细胞的两极分化决定了对atherogenic或antiatherogenic的结果.
- 树突细胞 (DCs) 调节免疫反应和耐受性,但它们在动脉样硬化中的作用尚不清楚.
研究的目的:
- 定义传统树突细胞 (DCs) 在动脉样硬化中的作用.
- 调查调节DC寿命和免疫性如何影响动脉动脉生成.
- 探索DCs,免疫反应和胆固醇平衡之间的关系.
主要方法:
- 使用CD11c促进器驱动的hBcl-2过度表达,创建了一个具有增强DC寿命和免疫性 (DC-hBcl2小鼠) 的小鼠模型.
- 研究了DC-hBcl2小鼠在低密度脂蛋白受体缺乏或无脂蛋白E缺乏的背景.
- 在高脂血症小鼠中减少了DCs,以评估它们对胆固醇血症的影响.
主要成果:
- 在DC-hBcl2小鼠中,扩大的DC种群显示T细胞激活增强,T助手1/17细胞因子配置,以及对氧化特异性表位体的自身抗体增加.
- 尽管有益动脉原性免疫特征,但DC扩张与降低血胆固醇水平和没有加速斑块进展有悖论的联系.
- 在高脂血症小鼠中,DC的耗尽导致胆固醇血量增加,支持DC水平和胆固醇调节之间的联系.
结论:
- 传统的DC是动脉样硬化过程中不可或缺的组成部分.
- DCs直接参与调节胆固醇稳态和动脉样硬化的免疫反应.
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