约翰霍普金斯大学医学院研究团队报道了肥大细胞受体通过硬脑膜轴介导中风后脑炎症。相关论文于2025年7月24日发表于国际顶尖学术期刊《细胞》杂志上。

该课题组人员发现肥大细胞特异性受体Mrgprb2调节中风后脑膜的脑炎症。Mrgprb2促进脑卒中后脑膜肥大细胞脱颗粒，释放免疫介质。这一过程将颅骨骨髓中性粒细胞招募到硬脑膜，并通过切断化学排斥信号蛋白3a进一步促进中性粒细胞从硬脑膜向大脑的迁移。课题组研究人员证明，人类同源基因MRGPRX2在人脑膜肥大细胞中表达，并通过中风后神经肽物质P的上调而激活。药理学抑制Mrgprb2可减少脑卒中后炎症，改善小鼠神经预后，提供可药物靶点。总的来说，他们的研究确定了Mrgprb2是免疫从颅骨骨髓库迁移到大脑的关键脑膜看门人。

据了解，大脑周围的免疫环境在监测损伤迹象方面起着重要作用。包括缺血性中风在内的损伤可破坏这种平衡并引发夸张的炎症反应，但其潜在机制尚不清楚。

附：英文原文

Title: A mast cell receptor mediates post-stroke brain inflammation via a dural-brain axis

Author: Ruchita Kothari, Mostafa W. Abdulrahim, Hyun Jong Oh, Daniel H. Capuzzi, Collin B. Kilgore, Sumil K. Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S. Saini, Jennifer E. Kim, Justin M. Caplan, Fernanado L. Gonzalez, Christopher M. Jackson, Chetan Bettegowda, Judy Huang, Bhanu P. Ganesh, Chunfeng Tan, Raymond C. Koehler, Rafael J. Tamargo, Louise D. McCullough, Risheng Xu, Xinzhong Dong

Issue&Volume: 2025-07-24

Abstract: The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal mast cells and is activated by upregulation of the neuropeptide substance P following stroke. Pharmacologically inhibiting Mrgprb2 reduces post-stroke inflammation and improves neurological outcomes in mice, providing a druggable target. Collectively, our study identifies Mrgprb2 as a critical meningeal gatekeeper for immune migration from skull bone marrow reservoirs into the brain.

DOI: 10.1016/j.cell.2025.06.045

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00747-0