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Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation
Developmental Cell ( IF 11.8 ) Pub Date : 2020-10-09 , DOI: 10.1016/j.devcel.2020.09.020
Jin Cui 1 , Frederick B Shipley 2 , Morgan L Shannon 1 , Osama Alturkistani 3 , Neil Dani 1 , Mya D Webb 1 , Arthur U Sugden 4 , Mark L Andermann 5 , Maria K Lehtinen 2
Affiliation  

The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized “hotspots” at the distal tips of ChP villi. In vivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults.



中文翻译:

母体免疫激活后胚胎脉络丛屏障的炎症

脉络丛 (ChP) 通过分泌指导性线索和提供保护性脑屏障来调节大脑发育。在这里,我们展示了 polyI:C 介导的母体免疫激活导致发育中的小鼠胚胎大脑中的炎症反应,表现为促炎脑脊液 (CSF) 和 ChP 巨噬细胞的积累。CSF-CCL2 的升高足以驱动 ChP 免疫细胞的募集、激活和增殖。此外,ChP 巨噬细胞放弃了它们的常规平铺模式,并重新定位到无 ChP 边缘,在那里它们破坏了减弱的上皮屏障。我们进一步发现,这些免疫细胞通过 ChP 绒毛远端尖端解剖学上专门的“热点”从 ChP 进入大脑。体内双光子成像表明,在胚胎发生的早期阶段,ChP 巨噬细胞的监视行为已经出现。因此,胚胎 ChP 形成了一个功能性脑屏障,可以对外部侮辱产生炎症反应。

更新日期:2020-12-07
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