美国西北大学David Gate研究组发现健康大脑衰老和认知障碍过程中的脑脊液免疫失调。2022年12月13日，国际知名学术期刊《细胞》发表了这一成果。
研究人员对45名认知正常的受试者的脑脊液（CSF）进行了单细胞RNA测序，范围从54岁到82岁。研究人员发现，随着年龄的增长，单核细胞中的脂质运输基因出现了上调。然后研究人员将这一队列与14名认知障碍的受试者进行了比较。在认知障碍者中，单核细胞中脂质转运基因的下调与CD8 T细胞的细胞因子信号的改变同时发生。认知障碍者的克隆CD8 T效应记忆细胞上调了C-X-C模体趋化因子受体6（CXCR6）。
认知障碍受试者的CSF中CXCR6配体——C-C动化学因子配体16（CXCL16）升高，表明CXCL16-CXCR6信号是抗原特异性T细胞进入大脑的一种机制。因此，这些结果揭示了在健康的大脑衰老和认知障碍过程中脑脊液的免疫失调。
据介绍，CSF包含一个严格调节的免疫系统。然而，关于CSF免疫力是如何随着衰老或神经退行性疾病而改变的知识还很缺乏。
附：英文原文
Title: Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment
Author: Natalie Piehl, Lynn van Olst, Abhirami Ramakrishnan, Victoria Teregulova, Brooke Simonton, Ziyang Zhang, Emma Tapp, Divya Channappa, Hamilton Oh, Patricia M. Losada, Jarod Rutledge, Alexandra N. Trelle, Elizabeth C. Mormino, Fanny Elahi, Douglas R. Galasko, Victor W. Henderson, Anthony D. Wagner, Tony Wyss-Coray, David Gate
Issue&Volume: 2022-12-13
Abstract: Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity is altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on CSF from 45 cognitively normal subjects ranging from 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes with age. We then compared this cohort with 14 cognitively impaired subjects. In cognitively impaired subjects, downregulation of lipid transport genes in monocytes occurred concomitantly with altered cytokine signaling to CD8 T cells. Clonal CD8 T effector memory cells upregulated C-X-C motif chemokine receptor 6 (CXCR6) in cognitively impaired subjects. The CXCR6 ligand, C-X-C motif chemokine ligand 16 (CXCL16), was elevated in the CSF of cognitively impaired subjects, suggesting CXCL16-CXCR6 signaling as a mechanism for antigen-specific T cell entry into the brain. Cumulatively, these results reveal cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment.
DOI: 10.1016/j.cell.2022.11.019
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01463-5