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Apolipoprotein E receptor 2 deficiency decreases endothelial adhesion of monocytes and protects against autoimmune encephalomyelitis
Science Immunology ( IF 17.6 ) Pub Date : 2021-08-27 , DOI: 10.1126/sciimmunol.abd0931
Laurent Calvier 1, 2 , Navid Manouchehri 3 , Anastasia Sacharidou 4 , Chieko Mineo 4 , Philip W Shaul 4 , David Y Hui 5 , Maria Z Kounnas 6 , Olaf Stüve 3, 7 , Joachim Herz 1, 2, 3, 8
Affiliation  

Under normal conditions, the blood-brain barrier effectively regulates the passage of immune cells into the central nervous system (CNS). However, under pathological conditions such as multiple sclerosis (MS), leukocytes, especially monocytes, infiltrate the CNS where they promote inflammatory demyelination, resulting in paralysis. Therapies targeting the immune cells directly and preventing leukocyte infiltration exist for MS but may compromise the immune system. Here, we explore how apolipoprotein E receptor 2 (ApoER2) regulates vascular adhesion and infiltration of monocytes during inflammation. We induced experimental autoimmune encephalitis in ApoER2 knockout mice and in mice carrying a loss-of-function mutation in the ApoER2 cytoplasmic domain. In both models, paralysis and neuroinflammation were largely abolished as a result of greatly diminished monocyte adherence due to reduced expression of adhesion molecules on the endothelial surface. Our findings expand our mechanistic understanding of the vascular barrier, the regulation of inflammation and vascular permeability, and the therapeutic potential of ApoER2-targeted therapies.



中文翻译:


载脂蛋白 E 受体 2 缺陷会降低单核细胞的内皮粘附力并预防自身免疫性脑脊髓炎



正常情况下,血脑屏障有效调节免疫细胞进入中枢神经系统(CNS)。然而,在多发性硬化症(MS)等病理条件下,白细胞,尤其是单核细胞,会浸润中枢神经系统,促进炎症脱髓鞘,导致瘫痪。针对多发性硬化症,存在直接针对免疫细胞并防止白细胞浸润的疗法,但可能会损害免疫系统。在这里,我们探讨载脂蛋白 E 受体 2 (ApoER2) 在炎症过程中如何调节单核细胞的血管粘附和浸润。我们在 ApoER2 敲除小鼠和 ApoER2 胞质结构域携带功能丧失突变的小鼠中诱导实验性自身免疫性脑炎。在这两种模型中,由于内皮表面粘附分子表达减少,单核细胞粘附大大减少,麻痹和神经炎症基本上被消除。我们的研究结果扩展了我们对血管屏障、炎症和血管通透性调节以及 ApoER2 靶向疗法的治疗潜力的机制理解。

更新日期:2021-08-29
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