Huang Yilin, Liu Huisheng, Hu Jiaqi, Han Chongyin, Zhong Zhenggang, Luo Wei, Zhang Yuhu, Ling Fei
School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
Clinical Research Institute, Foshan Hospital, Sun Yat-sen University, Foshan, China.
Front Aging Neurosci. 2021 Aug 17;13:686066. doi: 10.3389/fnagi.2021.686066. eCollection 2021.
Parkinson's disease (PD) is the second most neurodegenerative disease in the world. T cell infiltration in the central nervous system (CNS) has provided insights that the peripheral immune cells participate in the pathogenesis of PD. However, the association between the peripheral immune system and CNS remains to be elucidated. In this study, we analyzed incorporative substantia nigra (SN) expression data and blood expression data using the CIBERSORT to obtain the 22 immune cell fractions and then explored the molecular function to identify the potential key immune cell types and genes of PD. We observed that the proportions of naïve CD4 T cells, gamma delta T cells, resting natural killer (NK) cells, neutrophils in the blood, and regulatory T cells (Tregs) in the SN were significantly different between patients with PD and healthy controls (HCs). We identified p53-induced death domain protein 1 () as the hub gene of a PD-related module. The enrichment score of the neuron-specific gene set was significantly different between PD and HC, and genes in the neuron-related module were enriched in the biological process about mitochondria and synapses. These results suggested that the fractions of naïve CD4 T cells, gamma delta T cells, resting NK cells, and neutrophils may be used as a combined diagnostic marker in the blood, and Tregs in SN may be a potential therapeutic design target for PD.
帕金森病（PD）是世界上第二常见的神经退行性疾病。中枢神经系统（CNS）中的T细胞浸润提示外周免疫细胞参与了PD的发病机制。然而，外周免疫系统与CNS之间的关联仍有待阐明。在本研究中，我们使用CIBERSORT分析整合的黑质（SN）表达数据和血液表达数据，以获得22种免疫细胞亚群，然后探索分子功能，以确定PD潜在的关键免疫细胞类型和基因。我们观察到，PD患者与健康对照（HCs）之间，血液中幼稚CD4 T细胞、γδ T细胞、静息自然杀伤（NK）细胞、中性粒细胞以及SN中调节性T细胞（Tregs）的比例存在显著差异。我们将p53诱导死亡结构域蛋白1（ ）鉴定为与PD相关模块的枢纽基因。PD和HC之间神经元特异性基因集的富集分数存在显著差异，且神经元相关模块中的基因在关于线粒体和突触的生物学过程中富集。这些结果表明，幼稚CD4 T细胞、γδ T细胞、静息NK细胞和中性粒细胞的亚群可能作为血液中的联合诊断标志物，而SN中的Tregs可能是PD潜在的治疗设计靶点。
