JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
Mediators Inflamm. 2013;2013:898165. doi: 10.1155/2013/898165. Epub 2013 Aug 6.
The central nervous system (CNS) is an immune-privileged environment protected by the blood-brain barrier (BBB), which consists of specific endothelial cells that are brought together by tight junctions and tight liner sheets formed by pericytes and astrocytic end-feet. Despite the BBB, various immune and tumor cells can infiltrate the CNS parenchyma, as seen in several autoimmune diseases like multiple sclerosis (MS), cancer metastasis, and virus infections. Aside from a mechanical disruption of the BBB like trauma, how and where these cells enter and accumulate in the CNS from the blood is a matter of debate. Recently, using experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we found a "gateway" at the fifth lumber cord where pathogenic autoreactive CD4+ T cells can cross the BBB. Interestingly, this gateway is regulated by regional neural stimulations that can be mechanistically explained by the gate theory. In this review, we also discuss this theory and its potential for treating human diseases.
中枢神经系统（CNS）是一个免疫特权环境，由血脑屏障（BBB）保护，血脑屏障由紧密连接的特定内皮细胞组成，由周细胞和星形胶质细胞的终足形成紧密线性片。尽管有 BBB，各种免疫细胞和肿瘤细胞仍可以渗透到中枢神经系统实质中，如多发性硬化症（MS）、癌症转移和病毒感染等几种自身免疫性疾病中。除了创伤等 BBB 的机械破坏外，这些细胞如何以及从血液中何处进入和积聚到中枢神经系统仍然存在争议。最近，我们使用实验性自身免疫性脑脊髓炎（EAE），即 MS 的动物模型，在第五腰椎发现了一个“门户”，致病性自身反应性 CD4+T 细胞可以穿过血脑屏障。有趣的是，这个门户受到区域神经刺激的调节，其机制可以用门控理论来解释。在这篇综述中，我们还讨论了该理论及其在治疗人类疾病方面的潜在应用。
