通过蛋白C受体呈现的脂质将凝血与自身免疫联系在一起
Nadine Müller-Calleja1,2,3, Anne Hollerbach1,2, Jennifer Royce3
1Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany.
Science (New York, N.Y.)
|March 12, 2021
概括
抗脂抗体 (aPLs) 针对免疫细胞上的脂蛋白复合体,导致自身免疫性疾病. 阻断这种与EPCR-LBPA信号的相互作用可以减少小鼠的血栓形成和狼症状.
科学领域:
- 免疫学
- 自体免疫性
- 血管生物学
背景情况:
- 抗脂抗体 (aPLs) 是严重自身免疫疾病的关键驱动因素,包括血管病理和妊娠并发症.
- 细胞表面的精确目标和aPL的信号机制仍然不完全理解,阻碍了治疗的发展.
研究的目的:
- 通过aPLs识别特定的细胞表面抗原.
- 阐明这种抗原在aPL介导的血栓形成和炎症信号传递中的作用.
- 在临床前模型中评估针对该抗原的治疗潜力.
主要方法:
- 通过内皮蛋白C受体 (EPCR) 作为向抗原呈现的内体双酸 (LBPA) 的鉴定.
- 对aPL与EPCR-LBPA在先天免疫细胞上的接触进行分析.
- 评估干扰素和类似受体的7依赖B1a细胞扩张和自身抗体的产生.
- 在系统性红斑狼的小鼠模型中抑制EPCR-LBPA信号.
主要成果:
- aPLs在先天免疫细胞上识别EPCR-LBPA复合体,从而启动内体炎症信号.
- 这种相互作用维持了B1a细胞的扩张和自身抗体的产生,延续了自我增强的自身免疫循环.
- 在小鼠模型中,EPCR-LBPA信号的药理性中断显著减弱了aPL诱导的病态和自身免疫.
结论:
- EPCR-LBPA复合体是致病性aPLs的关键细胞表面标.
- 针对EPCR-LBPA相互作用为抗脂综合征和相关自身免疫性疾病提供了一个有前途的治疗策略.
- 这一发现揭示了自身免疫性疾病延续的新机制,
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