Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, The Netherlands.
Department of Pathology, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Acta Neuropathol Commun. 2020 Feb 3;8(1):9. doi: 10.1186/s40478-020-0885-1.
The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.
脉络丛(CP)位于外周血液和脑脊液之间,参与中枢神经系统(CNS)的内环境稳定调节。在多发性硬化症(MS)中,CNS 发生脱髓鞘和炎症。虽然 MS 的实验动物模型指出 CP 是免疫细胞入侵 CNS 的主要途径,但对于 MS 进行性阶段 CP 中免疫细胞的分布知之甚少。在这里,我们使用免疫组织化学和共聚焦显微镜技术,根据在不同 CP 隔室中的丰度和位置,来探索进行性 MS 患者和非神经炎症对照者 CP 中的主要免疫细胞群体。我们首次表明,与对照组相比,进行性 MS 患者 CP 中的粒细胞和 CD8+T 细胞的基质密度更高。与先前的研究一致,CP 中的巨噬细胞和树突状细胞数量相对较高。此外,我们在 CP 中几乎没有发现 B 细胞或浆细胞。MHCII+抗原呈递细胞通常与 T 细胞密切相关,这表明 CP 具有中枢神经系统免疫监测功能。总的来说,我们的数据强调了 CP 在免疫稳态中的作用,并表明进行性 MS 患者 CP 中存在轻微的炎症过程。然而,我们的发现表明 CP 仅在慢性 MS 中免疫细胞向 CNS 迁移中起次要作用。