Sequential infiltration of Th17 cells into the substantia nigra in a primate model of Parkinson's disease

Abstract

Parkinson’s disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Recent studies have focused on the dysregulation of CD4+ T cell subsets, including Th17 cells, with nigrostriatal dopaminergic neurodegeneration in PD. Nonetheless, the mechanisms behind the sequential and sustained infiltration of these T cell subsets into the brain during PD progression are not well understood. This study aimed to elucidate the long-term infiltration patterns of Th1, Th2, and Th17 cells in the SN during PD progression. After injecting cynomolgus monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to develop a non-human primate model of PD, we observed dopaminergic neuronal loss and infiltration patterns of CD4+ T cell subsets in the SN at early, intermediate, and late phases. Th17 cells were observed to infiltrate immediately during the early phase, unlike the delayed infiltration observed for Th1 and Th2 cells. Notably, the early phase infiltration of Th17 cells coincides with the rapid degeneration of dopaminergic neurons. Furthermore, the physical proximity between Th17 lymphocytes and a decreased number of dopaminergic neurons was observed in the SN after MPTP injection. This study reinforces that Th17 cells are associated with neurodegeneration of dopaminergic neurons in the onset of PD.