自体抗原蛋白-DNA复合体刺激血类树突细胞,促进动脉样硬化
Yvonne Döring1, Helga D Manthey, Maik Drechsler
1Rudolf Virchow Center, DFG Research Center for Experimental Medicine, University of Würzburg, Josef-Schneider Strasse 2, Würzburg, Germany.
Circulation
|March 6, 2012
概括
血细胞树突细胞 (pDCs) 通过对自身DNA和抗菌的反应,促进炎症和斑块生长,促进动脉动脉样硬化. 针对这些途径可能为动脉样硬化提供新的治疗策略.
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
- 动脉样硬化的发病因子
背景情况:
- 炎症是动脉样硬化和自身免疫过程的关键因素.
- 血细胞树突细胞 (pDCs) 产生I型干扰子,并能感知自身DNA,但它们在动脉样硬化中的作用尚不清楚.
研究的目的:
- 研究pDCs在动脉样硬化的发展和进展中的作用.
- 探索pDCs在动脉样硬化病变中促进自身免疫反应的机制.
主要方法:
- 在小鼠和人类动脉样硬化病变中检测pDCs.
- 评估pDC细胞酶和T细胞原始化对改性LDL的反应.
- 在动脉样硬化动脉中分析/DNA复合体,中性粒细胞外陷和干扰素-α.
- 在pDC枯竭,克兰普缺陷或克兰普/DNA复合物管理的小鼠模型中评估动脉样硬化和抗体标位.
- 抗dsDNA抗体水平与人类患者疾病严重程度的相关性.
主要成果:
- 在动脉样硬化病变中存在pDCs,其细胞能力由修饰的LDL增强.
- /DNA复合体刺激pDCs产生干扰素-α;增加和中性粒细胞外细胞陷在动脉样硬化动脉中发现.
- /DNA复合体会加剧动脉样硬化,而pDC耗尽和缺乏会减少病变形成和抗dsDNA抗体标位.
- pDC激活和干扰素α治疗促进斑块生长并增加抗dsDNA抗体水平.
- 在患有症状与无症状动脉狭窄症患者中观察到抗dsDNA抗体的升高.
结论:
- 动脉样硬化病变中的自我DNA和/LL37刺激了pDC驱动的自身免疫通路.
- 这一途径产生抗双链DNA抗体,加剧动脉样硬化.
- pDCs,自我DNA和Cramp/LL37代表了动脉样硬化的潜在新型治疗标.
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