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

Abstract：

: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 oxidative stress-induced MHC-I presentation. All animal experiments were approved by the Southern Medical University Ethics Committee (No. 81802040, approved on February 25, 2018).

journal_name

Neural Regen Res

journal_title

Neural regeneration research

authors

Wang BY,Ye YY,Qian C,Zhang HB,Mao HX,Yao LP,Sun X,Lu GH,Zhang SZ

doi

10.4103/1673-5374.313057

keywords:

["CD8+T cell","PINK1\n","Parkinson's disease","antigen presentation","autoimmune","dopaminergic neuron","major histocompatibility complex class I","mitochondria","neuroinflammation","oxidative stress"]

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

2521-2527

issue

eissn

1673-5374

issn

1876-7958

pii

NeuralRegenRes_2021_16_12_2521_313057

journal_volume

pub_type

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