PDF(Pubmed)
Abstract：
In recent decades there has been a large focus on understanding the mechanisms of peripheral immune cell infiltration into the central nervous system (CNS) in neuroinflammatory diseases. This intense research led to several immunomodulatory therapies to attempt to regulate immune cell infiltration at the blood brain barrier (BBB), the choroid plexus (ChP) epithelium, and the glial barrier. The fate of these infiltrating immune cells depends on both the neuroinflammatory environment and their type-specific interactions with innate cells of the CNS. Although the fate of the majority of tissue infiltrating immune cells is death, a percentage of these cells could become tissue resident immune cells. Additionally, key populations of immune cells can possess the ability to \"drain\" out of the CNS and act as messengers reporting signals from the CNS toward peripheral lymphatics. Recent data supports that the meningeal lymphatic system is involved not just in fluid homeostatic functions in the CNS but also in facilitating immune cell migration, most notably dendritic cell migration from the CNS to the meningeal borders and to the draining cervical lymph nodes. Similar to the peripheral sites, draining immune cells from the CNS during neuroinflammation have the potential to coordinate immunity in the lymph nodes and thus influence disease. Here in this review, we will evaluate evidence of immune cell drainage from the brain via the meningeal lymphatics and establish the importance of this in animal models and humans. We will discuss how targeting immune cells at sites like the meningeal lymphatics could provide a new mechanism to better provide treatment for a variety of neurological conditions.
摘要：
近几十年来，人们非常关注了解神经炎症性疾病中外周免疫细胞渗入中枢神经系统（CNS）的机制。这项深入的研究导致了几种免疫调节疗法试图调节血脑屏障（BBB）的免疫细胞浸润，脉络丛（ChP）上皮，和神经胶质屏障。这些浸润免疫细胞的命运取决于神经炎症环境及其与CNS先天细胞的类型特异性相互作用。尽管大多数组织浸润免疫细胞的命运是死亡，这些细胞中的一定百分比可以成为组织驻留的免疫细胞。此外,免疫细胞的关键群体可以具有“排出”中枢神经系统的能力，并作为信使报告信号从中枢神经系统到外周淋巴管。最近的数据支持，脑膜淋巴系统不仅参与中枢神经系统的体液稳态功能，而且还促进免疫细胞迁移，最值得注意的是树突状细胞从中枢神经系统迁移到脑膜边界和引流的颈部淋巴结。类似于外围站点，在神经炎症期间从CNS排出免疫细胞有可能协调淋巴结中的免疫力，从而影响疾病。在这篇评论中，我们将评估免疫细胞通过脑膜淋巴管从大脑引流的证据，并确定这在动物模型和人类中的重要性。我们将讨论如何在脑膜淋巴管等部位靶向免疫细胞可以提供一种新的机制，以更好地为各种神经系统疾病提供治疗。
