Stress increases MHC-I expression in dopaminergic neurons and induces autoimmune activation in Parkinson’s disease  

作　　者：Bao-Yan Wang Yong-Yi Ye Chen Qian Hong-Bo Zhang Heng-Xu Mao Long-Ping Yao Xiang Sun Guo-Hui Lu Shi-Zhong Zhang 

机构地区：[1]The National Key Clinical Specialty,The Engineering Technology Research Center of Education Ministry of China,Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration,Department of Neurosurgery,Zhujiang Hospital,Southern Medical University,Guangzhou,Guangdong Province,China [2]Department of Neurosurgery,the Second Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong Province,China [3]Department of Neurosurgery,First Affiliated Hospital of Nanchang University,Nanchang,Jiangxi Province,China

出　　处：《Neural Regeneration Research》2021年第12期2521-2527,共7页中国神经再生研究（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China,Nos.81671240(to SZZ),81560220(to GHL);the Youth Science Foundation of Jiangxi Province of China,No.20151BAB215014(to GHL);Health and Family Planning Commission of Jiangxi Province of China,No.20195109(to GHL)。

摘　　要：The expression of major histocompatibility complex class I(MHC-I),a key antigen-presenting protein,can be induced in dopaminergic neurons in the substantia nigra,thus indicating its possible involvement in the occurrence and development of Parkinson’s disease.However,it remains unclear whether oxidative stress induces Parkinson’s disease through the MHC-I pathway.In the present study,polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium(MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson’s disease mouse model.The findings revealed that MHC-I was expressed in both models.To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells,immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8(CD8)+T cell infiltration in the substantia nigra of MPTP-treated mice.The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+T cells.Moreover,in MPTP-induced Parkinson’s disease model mice,the genetic knockdown of endogenous MHC-I,which was caused by injecting specific adenovirus into the substantia nigra,led to a significant reduction in CD8+T cell infiltration and alleviated dopaminergic neuronal death.To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation,the expression of PTEN-induced kinase 1(PINK1)was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA(siRNA),and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells.Taken together,MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation,thus rendering dopaminergic neurons susceptible to immune cells and degeneration.This may be one of the mechanisms of oxidative stress-induced Parkinson’s disease,and implies the potential neuroprotective role of PINK1 in oxida

关 键 词：antigen presentation AUTOIMMUNE CD8+T cell dopaminergic neuron major histocompatibility complex class I mitochondria NEUROINFLAMMATION oxidative stress Parkinson’s disease PINK1 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]