Immune cells as messengers from the CNS to the periphery: the role of the meningeal lymphatic system in immune cell migration from the CNS.
Immune cells as messengers from the CNS to the periphery: the role of the meningeal lymphatic system in immune cell migration from the CNS.
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DOI：
10.3389/fimmu.2023.1233908
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
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近几十年来，人们一直关注了解外周免疫细胞浸润到中枢神经系统（CNS）中的神经炎性疾病的机制。这种密集的研究导致了几种免疫调节疗法，试图调节血脑屏障（BBB）、脉络丛（ChP）上皮和神经胶质屏障处的免疫细胞浸润。这些浸润性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。虽然大多数组织浸润免疫细胞的命运是死亡，但这些细胞中的一部分可以成为组织驻留免疫细胞。此外，免疫细胞的关键群体可以具有从CNS“排出”的能力，并充当从CNS向外周神经系统报告信号的信使。最近的数据支持脑膜淋巴系统不仅参与CNS中的流体稳态功能，而且还促进免疫细胞迁移，最显著的是树突状细胞从CNS迁移到脑膜边界和引流颈淋巴结。与外周部位类似，神经炎症期间从CNS排出的免疫细胞具有协调淋巴结中的免疫的潜力，从而影响疾病。在这篇综述中，我们将评估免疫细胞通过脑膜炎从大脑中引流的证据，并确定这在动物模型和人类中的重要性。我们将讨论如何将免疫细胞靶向到脑膜炎等部位，从而提供一种新的机制，更好地为各种神经系统疾病提供治疗。
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.