小柯机器人

科学家首次在脑脊膜中发现受肠道训练的免疫细胞类型
2020-11-08 15:25

英国剑桥大学Menna R. Clatworthy、美国国立卫生研究院Dorian B. McGavern等研究人员合作发现,肠道训练的IgA浆细胞捍卫脑脊膜静脉窦。相关论文于2020年11月4日在线发表在《自然》杂志上。

研究人员发现,在体内平衡过程中,小鼠和人类脑脊膜含有分泌IgA的浆细胞。这些细胞位于硬脑膜静脉窦附近:缓血流区域可能会使得血源性病原体进入大脑。窦周围IgA浆细胞随着年龄的增长和肠屏障的破坏而增加。
 
相反,它们在无菌小鼠中却很少,但是通过肠道重新定殖可以恢复它们的存在。B细胞受体测序证实脑脊膜IgA+细胞起源于肠道。脑脊膜浆细胞的特定耗竭或IgA缺乏导致静脉窦感染后减少了窦周围区域的真菌截留并增加了在脑中的扩散,这表明脑脊膜IgA对于在此脆弱的静脉屏障表面捍卫中枢神经系统至关重要。
 
据介绍,中枢神经系统曾经被认为是免疫豁免的部位,但是最近的数据表明,脑脊膜(围绕大脑和脊髓的膜)包含多种免疫细胞。迄今为止,研究集中在巨噬细胞和T细胞上,但尚未包括对脑膜体液免疫的详细分析。
 
附:英文原文

Title: Gut-educated IgA plasma cells defend the meningeal venous sinuses

Author: Zachary Fitzpatrick, Gordon Frazer, Ashley Ferro, Simon Clare, Nicolas Bouladoux, John Ferdinand, Zewen Kelvin Tuong, Maria Luciana Negro-Demontel, Nitin Kumar, Ondrej Suchanek, Tamara Tajsic, Katherine Harcourt, Kirsten Scott, Rachel Bashford-Rogers, Adel Helmy, Daniel S. Reich, Yasmine Belkaid, Trevor D. Lawley, Dorian B. McGavern, Menna R. Clatworthy

Issue&Volume: 2020-11-04

Abstract: The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges—the membranes that surround the brain and spinal cord—contain a diverse population of immune cells1. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain2. Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA+ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.

DOI: 10.1038/s41586-020-2886-4

Source: https://www.nature.com/articles/s41586-020-2886-4

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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