实质边界巨噬细胞调节脑脊液的流动动态

美国圣路易斯华盛顿大学Jonathan Kipnis等研究人员合作发现，实质边界巨噬细胞调节脑脊液的流动动态。2022年11月9日，《自然》杂志在线发表了这项成果。

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研究人员表示，巨噬细胞是维持组织稳态的重要角色。血管周围和脑膜巨噬细胞居住在中枢神经系统（CNS）实质附近，它们在中枢神经系统生理学中的作用还没有被充分研究。鉴于它们与脑脊液（CSF）的持续互动和战略定位，研究人员将这些细胞统称为实质边界巨噬细胞（PBM）。

研究人员证明了PBM调节CSF的流动动态。研究人员确定了一个表达高水平CD163和LYVE1（清道夫受体蛋白）的PBM亚群，与脑动脉树密切相关，并显示LYVE1+ PBM调节驱动CSF流动的动脉运动。药物或基因耗竭PBM导致细胞外基质蛋白的积累，阻碍CSF进入血管周围空间，并损害CNS的灌注和清除。

衰老相关的PBM的改变和CSF动态的损害在注射巨噬细胞集落刺激因子后得以恢复。从阿尔茨海默病（AD）患者和非AD患者获得的单核RNA测序数据表明，PBM的吞噬作用、内吞作用和干扰素-γ信号存在变化，这些途径在AD的小鼠模型中得到证实。

总之，这些研究结果确定PBM是CSF流动动态的新型细胞调节因子，并可以通过药物治疗来缓解与衰老和AD相关的大脑清除障碍。

附：英文原文

Title: Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid

Author: Drieu, Antoine, Du, Siling, Storck, Steffen E., Rustenhoven, Justin, Papadopoulos, Zachary, Dykstra, Taitea, Zhong, Fenghe, Kim, Kyungdeok, Blackburn, Susan, Mamuladze, Tornike, Harari, Oscar, Karch, Celeste M., Bateman, Randall J., Perrin, Richard, Farlow, Martin, Chhatwal, Jasmeer, Hu, Song, Randolph, Gwendalyn J., Smirnov, Igor, Kipnis, Jonathan

Issue&Volume: 2022-11-09

Abstract: Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1+ PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer’s disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD.

DOI: 10.1038/s41586-022-05397-3

Source: https://www.nature.com/articles/s41586-022-05397-3

来源：科学网小柯机器人