Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Exp Med. 2012 Jul 2;209(7):1325-34. doi: 10.1084/jem.20101974. Epub 2012 Jun 25.
Comparison of transcriptomic and proteomic data from pathologically similar multiple sclerosis (MS) lesions reveals down-regulation of CD47 at the messenger RNA level and low abundance at the protein level. Immunohistochemical studies demonstrate that CD47 is expressed in normal myelin and in foamy macrophages and reactive astrocytes within active MS lesions. We demonstrate that CD47(-/-) mice are refractory to experimental autoimmune encephalomyelitis (EAE), primarily as the result of failure of immune cell activation after immunization with myelin antigen. In contrast, blocking with a monoclonal antibody against CD47 in mice at the peak of paralysis worsens EAE severity and enhances immune activation in the peripheral immune system. In vitro assays demonstrate that blocking CD47 also promotes phagocytosis of myelin and that this effect is dependent on signal regulatory protein α (SIRP-α). Immune regulation and phagocytosis are mechanisms for CD47 signaling in autoimmune neuroinflammation. Depending on the cell type, location, and disease stage, CD47 has Janus-like roles, with opposing effects on EAE pathogenesis.
比较组织病理学相似的多发性硬化症（MS）病变的转录组学和蛋白质组学数据，揭示信使 RNA 水平的 CD47 下调和蛋白质水平的低丰度。免疫组织化学研究表明，CD47 在正常髓鞘和活跃 MS 病变中的泡沫状巨噬细胞和反应性星形胶质细胞中表达。我们证明 CD47(-/-) 小鼠对实验性自身免疫性脑脊髓炎（EAE）具有抗性，主要是由于在用髓鞘抗原免疫后免疫细胞激活失败。相比之下，在瘫痪高峰期用针对 CD47 的单克隆抗体阻断小鼠中的 CD47 会加重 EAE 的严重程度并增强外周免疫系统中的免疫激活。体外检测表明，阻断 CD47 还可促进髓鞘的吞噬作用，并且该作用依赖于信号调节蛋白α（SIRP-α）。免疫调节和吞噬作用是自身免疫性神经炎症中 CD47 信号传导的机制。根据细胞类型、位置和疾病阶段，CD47 具有类似两面神的作用，对 EAE 发病机制有相反的影响。
