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Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells.
Acta Neuropathologica Communications ( IF 7.1 ) Pub Date : 2020-02-03 , DOI: 10.1186/s40478-020-0885-1
Sabela Rodríguez-Lorenzo 1 , Julia Konings 1 , Susanne van der Pol 1 , Alwin Kamermans 1 , Sandra Amor 2, 3 , Jack van Horssen 1 , Maarten E Witte 1 , Gijs Kooij 1 , Helga E de Vries 1, 4
Affiliation  

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.

中文翻译:

进行性多发性硬化中脉络丛的炎症:粒细胞和T细胞的积累。

脉络丛(CP)地位于外周血和脑脊液之间,并参与中枢神经系统(CNS)稳态的调节。在多发性硬化症(MS)中,中枢神经系统发生脱髓鞘和炎症。虽然MS的实验动物模型指出CP是中枢神经系统免疫细胞入侵的关键途径,但在MS的进展阶段,关于免疫细胞在人CP中的分布知之甚少。在这里,我们使用免疫组化和共聚焦显微镜研究了进行性MS患者和非神经炎性对照患者CP的主要免疫细胞群,它们在不同CP腔室内的丰度和位置均如此。我们首次显示,与对照组相比,进行性MS患者的粒细胞和CD8 + T细胞的CP基质密度更高。与之前的研究一致,对照组和进行性MS患者的CP均包含相对大量的巨噬细胞和树突状细胞。此外,我们发现CP中实际上没有B细胞或浆细胞。通常在T细胞附近发现MHCII +抗原呈递细胞,提示CP的组成型CNS免疫监测功能。总之,我们的数据突出了CP在免疫稳态中的作用,并表明了进行性MS患者CP中出现了轻度炎症过程。但是,我们的发现表明,CP仅少量参与免疫细胞迁移到慢性MS中的CNS中。对照和进行性MS患者的CP均包含相对大量的巨噬细胞和树突状细胞。此外,我们发现CP中实际上没有B细胞或浆细胞。通常在T细胞附近发现MHCII +抗原呈递细胞,提示CP的组成型CNS免疫监测功能。总之,我们的数据突出了CP在免疫稳态中的作用,并表明了进行性MS患者CP中出现了轻度炎症过程。但是,我们的发现表明,CP仅少量参与免疫细胞迁移到慢性MS中的CNS中。对照和进行性MS患者的CP均包含相对大量的巨噬细胞和树突状细胞。此外,我们发现CP中实际上没有B细胞或浆细胞。通常在T细胞附近发现MHCII +抗原呈递细胞,提示CP的组成型CNS免疫监测功能。总之,我们的数据突出了CP在免疫稳态中的作用,并表明了进行性MS患者CP中出现了轻度炎症过程。但是,我们的发现表明,CP仅少量参与免疫细胞迁移到慢性MS中的CNS中。通常在T细胞附近发现MHCII +抗原呈递细胞,提示CP的组成型CNS免疫监测功能。总之,我们的数据突出了CP在免疫稳态中的作用,并表明了进行性MS患者CP中出现了轻度炎症过程。但是,我们的发现表明,CP仅少量参与免疫细胞迁移到慢性MS中的CNS中。通常在T细胞附近发现MHCII +抗原呈递细胞,提示CP的组成型CNS免疫监测功能。总之,我们的数据突出了CP在免疫稳态中的作用,并表明了进行性MS患者CP中出现了轻度炎症过程。但是,我们的发现表明,CP仅少量参与免疫细胞迁移到慢性MS中的CNS中。
更新日期:2020-04-22
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