Lipid presentation by the protein C receptor links coagulation with autoimmunity.
Lipid presentation by the protein C receptor links coagulation with autoimmunity.
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蛋白C受体的脂质呈递将凝血与自身免疫联系起来。
DOI：
10.1126/science.abc0956
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
抗磷脂抗体（aPL）引起以血管病理和妊娠并发症为特征的严重自身免疫性疾病。在这里，我们确定内体lysobisphosphatidic酸（LBPA）提出的CD 1d样内皮蛋白C受体（EPCR）作为一种致病性细胞表面抗原的aPL诱导血栓形成和内体炎症信号。aPL与先天免疫细胞上表达的EPCR-LBPA的接合维持干扰素和toll样受体7依赖性B1 a细胞扩增和自身抗体产生。EPCR-LBPA信号传导的特异性药理学中断减弱了系统性红斑狼疮小鼠模型中主要APL引起的病理和自身免疫的发展。因此，aPL识别单细胞表面脂质-蛋白质受体复合物以使依赖于与先天免疫补体和凝血途径的合作的自放大自身免疫信号传导环永久化。EPCR介导抗磷脂抗体的病理学及其在自身免疫中的干扰素依赖性扩增。
Antiphospholipid antibodies (aPLs) cause severe autoimmune disease characterized by vascular pathologies and pregnancy complications. Here, we identify endosomal lysobisphosphatidic acid (LBPA) presented by the CD1d-like endothelial protein C receptor (EPCR) as a pathogenic cell surface antigen recognized by aPLs for induction of thrombosis and endosomal inflammatory signaling. The engagement of aPLs with EPCR–LBPA expressed on innate immune cells sustains interferon- and toll-like receptor 7-dependent B1a cell expansion and autoantibody production. Specific pharmacological interruption of EPCR–LBPA signaling attenuates major aPL-elicited pathologies and the development of autoimmunity in a mouse model of systemic lupus erythematosus. Thus, aPLs recognize a single cell surface lipid–protein receptor complex to perpetuate a self-amplifying autoimmune signaling loop dependent on the cooperation with the innate immune complement and coagulation pathways. EPCR mediates pathologies of antiphospholipid antibodies and their interferon-dependent expansion in autoimmunity.
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影响因子：
13.3
作者：
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82.9
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20.3
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