Alpha-Synuclein-Specific Regulatory T Cells Ameliorate Parkinson's Disease Progression in Mice.

Abstract

Parkinson's disease (PD) is a long-term neurodegenerative disease characterized by dopaminergic neuronal loss and the aggregation of alpha-synuclein (&#x3b1;-syn) in the brain. Cell therapy using regulatory T cells (Tregs) has therapeutic potential on PD progression in a mouse model; however, several challenges were associated with its applications. Here, we propose a strategy for &#x3b1;-syn specific Treg expansion (&#x3b1;-syn Treg). We presented &#x3b1;-syn to T cells via dendritic cells. This method increased the mobility of Tregs towards the site of abundant &#x3b1;-syn in vitro (< 0.01; &#x3b1;-syn Tregs versus polyclonal Tregs (poly Tregs)) and in vivo. Consequently, &#x3b1;-syn Tregs showed noteworthy neuroprotective effects against motor function deficits (< 0.05,< 0.01; &#x3b1;-syn Tregs versus poly Tregs), dopaminergic neuronal loss (< 0.001; &#x3b1;-syn Tregs versus poly Tregs), and &#x3b1;-syn accumulation (< 0.05; &#x3b1;-syn Tregs versus poly Tregs) in MPTP-induced PD mice. Furthermore, the adoptive transfer of &#x3b1;-syn Tregs exerted immunosuppressive effects on activated microglia, especially pro-inflammatory microglia, in PD mice. Our findings suggest that &#x3b1;-syn presentation may provide a significant improvement in neuroprotective activities of Tregs and suggest the effective clinical application of Treg therapy in PD.