PDF(Pubmed)
Abstract：
Demyelination due to autoreactive T cells and inflammation in the central nervous system are principal features of multiple sclerosis (MS), a chronic and highly disabling human disease affecting brain and spinal cord. Here, we show that treatment with apelin, a secreted peptide ligand for the G protein-coupled receptor APJ/Aplnr, is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Apelin reduces immune cell entry into the brain, delays the onset and reduces the severity of EAE. Apelin affects the trafficking of leukocytes through the lung by modulating the expression of cell adhesion molecules that mediate leukocyte recruitment. In addition, apelin induces the internalization and desensitization of its receptor in endothelial cells (ECs). Accordingly, protection against EAE major outcomes of apelin treatment are phenocopied by loss of APJ/Aplnr function, achieved by EC-specific gene inactivation in mice or knockdown experiments in cultured primary endothelial cells. Our findings highlight the importance of the lung-brain axis in neuroinflammation and indicate that apelin targets the transendothelial migration of immune cells into the lung during acute inflammation.
摘要：
由于自身反应性T细胞和中枢神经系统炎症引起的脱髓鞘是多发性硬化症（MS）的主要特征，一种影响大脑和脊髓的慢性和高度致残的人类疾病。这里,我们证明用apelin治疗，G蛋白偶联受体APJ/Aplnr的分泌肽配体，在实验性自身免疫性脑脊髓炎（EAE）中具有保护性，MS的动物模型Apelin减少免疫细胞进入大脑，延迟EAE的发作并降低EAE的严重程度。Apelin通过调节介导白细胞募集的细胞粘附分子的表达来影响白细胞通过肺的运输。此外,apelin诱导其受体在内皮细胞（EC）中的内化和脱敏。因此，对EAE的保护Apelin治疗的主要结果是APJ/Aplnr功能丧失，通过在小鼠中进行EC特异性基因失活或在培养的原代内皮细胞中进行敲除实验来实现。我们的发现强调了肺-脑轴在神经炎症中的重要性，并表明apelin在急性炎症期间靶向免疫细胞的跨内皮迁移到肺中。
