小柯机器人

美国马萨诸塞州总医院Rudolph E. Tanzi，Doo Yeon Kim和Mehdi Jorfi共同合作，近期取得重要工作进展。他们在3D人类神经免疫轴模型中研究发现，浸润CD8⁺ T细胞会加剧阿尔茨海默氏病病理。相关研究成果2023年8月24日在线发表于《自然—神经科学》杂志上。

据介绍，外周免疫细胞的大脑浸润及其与大脑驻留细胞的相互作用可能导致阿尔茨海默病（AD）病理学。

为了检测这些相互作用，研究人员开发了一个三维人类神经免疫轴模型，包括干细胞来源的神经元、星形胶质细胞和小胶质细胞，以及外周免疫细胞。与对照培养物相比，研究人员观察到选择性浸润到AD中的T细胞（但不是B细胞）和单核细胞的数量增加。CD8⁺ T细胞浸润到AD培养物中导致小胶质细胞活化增加、神经炎症和神经退行性病变。使用单细胞RNA测序，研究人员确定T细胞渗透到AD培养物中导致神经胶质细胞中干扰素-γ和神经炎症途径的诱导。研究人员发现C-X-C基序趋化因子配体10（CXCL10）及其受体CXCR3在AD培养物中调节T细胞浸润和神经元损伤中的关键作用。

总之，这一研究表明，这种人类神经免疫轴模型是研究外周免疫细胞在脑疾病中作用的有用工具。

附：英文原文

Title: Infiltrating CD8+ T cells exacerbate Alzheimer’s disease pathology in a 3D human neuroimmune axis model

Author: Jorfi, Mehdi, Park, Joseph, Hall, Clare K., Lin, Chih-Chung Jerry, Chen, Meng, von Maydell, Djuna, Kruskop, Jane M., Kang, Byunghoon, Choi, Younjung, Prokopenko, Dmitry, Irimia, Daniel, Kim, Doo Yeon, Tanzi, Rudolph E.

Issue&Volume: 2023-08-24

Abstract: Brain infiltration of peripheral immune cells and their interactions with brain-resident cells may contribute to Alzheimer’s disease (AD) pathology. To examine these interactions, in the present study we developed a three-dimensional human neuroimmune axis model comprising stem cell-derived neurons, astrocytes and microglia, together with peripheral immune cells. We observed an increase in the number of T cells (but not B cells) and monocytes selectively infiltrating into AD relative to control cultures. Infiltration of CD8+ T cells into AD cultures led to increased microglial activation, neuroinflammation and neurodegeneration. Using single-cell RNA-sequencing, we identified that infiltration of T cells into AD cultures led to induction of interferon-γ and neuroinflammatory pathways in glial cells. We found key roles for the C-X-C motif chemokine ligand 10 (CXCL10) and its receptor, CXCR3, in regulating T cell infiltration and neuronal damage in AD cultures. This human neuroimmune axis model is a useful tool to study the effects of peripheral immune cells in brain disease.

DOI: 10.1038/s41593-023-01415-3

Source: https://www.nature.com/articles/s41593-023-01415-3

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex