中山大学苏士成课题组发现，脉络丛肥大细胞驱动肿瘤相关的脑积水。该研究于2023年12月5日在线发表于国际一流学术期刊《细胞》。

利用单核RNA测序和空间转录组学，研究人员发现脉络丛中存在一个独特的肥大细胞群体，并在肿瘤相关的脑积水（TAH）期间急剧增加。遗传命运追踪和颅内肥大细胞特异性胰蛋白酶基因敲除显示，脉络丛肥大细胞（CPMC）通过胰蛋白酶-PAR2-FoxJ1途径破坏脉络丛上皮的纤毛，从而增加脑脊液分泌。

人类脉络丛中也存在肥大细胞。脑脊液中的色氨酸酶水平与TAH的临床严重程度密切相关。BMS-262084是一种胰蛋白酶抑制剂，它能穿过血脑屏障，在体内抑制TAH，并在人多能干细胞衍生的脉络丛类器官模型中减轻肥大细胞诱导的上皮纤毛损伤。总之，研究人员揭示了CPMC的功能，并为TAH提供了一种有吸引力的疗法。

据介绍，TAH是脑转移常见的致命并发症。虽然有人认为除了机械性梗阻外还有其他因素，但确切的机制尚不清楚。

附：英文原文

Title: Choroid plexus mast cells drive tumor-associated hydrocephalus

Author: Yiye Li, Can Di, Shijian Song, Yubo Zhang, Yiwen Lu, Jianyou Liao, Bingxi Lei, Jian Zhong, Kaihua Guo, Nu Zhang, Shicheng Su

Issue&Volume: 2023-12-05

Abstract: Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brainmetastases. Although other factors beyond mechanical obstructions have been suggested,the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatialtranscriptomics, we find that a distinct population of mast cells locate in the choroidplexus and dramatically increase during TAH. Genetic fate tracing and intracranialmast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs)disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway andconsequently increase cerebrospinal fluid production. Mast cells are also found inthe human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associatedwith clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross theblood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotentstem-cell-derived choroid plexus organoid model. Collectively, we uncover the functionof CPMCs and provide an attractive therapy for TAH.

DOI: 10.1016/j.cell.2023.11.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01182-0