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T 细胞失调与帕金森病的疾病严重程度有关。

T-cell dysregulation is associated with disease severity in Parkinson's Disease.

机构信息

Neurology, University Clinic, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.

出版信息

J Neuroinflammation. 2021 Oct 30;18(1):250. doi: 10.1186/s12974-021-02296-8.

DOI:10.1186/s12974-021-02296-8
PMID:34717679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8556877/
Abstract

The dysregulation of peripheral immunity in Parkinson's Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8 cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemagglutinin that also correlated with disease severity. In summary, our data suggest that the consequences of disease severity account for the changes in PD T cells, rather than age, age of onset, duration or the disease progression rate.

摘要

帕金森病(PD)外周免疫失调包括 T 细胞数量和基因表达的变化。PD 患者外周 T 细胞异常的存在已得到充分证实,但对于它们与临床参数(如年龄、发病年龄、进展速度或疾病严重程度)的关联了解较少。我们通过流式细胞术和 NanoString 基因表达分析,对 PD 患者和年龄匹配的健康对照者的横断面队列进行了详细的 T 细胞数量、基因表达和激活研究。我们表明,PD 血液中相对 T 细胞数量的明显减少主要是由 CD8 细胞毒性 T 细胞减少引起的,主要与疾病的严重程度有关。此外,我们还证明了 PD 患者 T 细胞中炎症基因的表达也与疾病严重程度有关。PD T 细胞在植物血凝素刺激下表现出更高的激活水平,这也与疾病严重程度相关。总之,我们的数据表明,疾病严重程度的后果导致了 PD T 细胞的变化,而不是年龄、发病年龄、持续时间或疾病进展速度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/340dbd8abd7f/12974_2021_2296_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/29350a6d2c75/12974_2021_2296_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/5a0af5421fcd/12974_2021_2296_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/915fe9e7d3a0/12974_2021_2296_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/340dbd8abd7f/12974_2021_2296_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/29350a6d2c75/12974_2021_2296_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/5a0af5421fcd/12974_2021_2296_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/915fe9e7d3a0/12974_2021_2296_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/227f/8556877/340dbd8abd7f/12974_2021_2296_Fig4_HTML.jpg

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CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease.CD4 T 细胞在帕金森病小鼠模型中介导脑部炎症和神经退行性变。
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Periphery and brain, innate and adaptive immunity in Parkinson's disease.
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