Alfa-sinüklein spesifik düzenleyici T hücreleri farelerde Parkinson hastalığı ilerlemesini hafifletir

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Abstract Parkinson’s disease (PD) is a long-term neurodegenerative disease characterized by dopaminergic neuronal loss and the aggregation of alpha-synuclein (α-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 α-syn specific Treg expansion. We presented α-syn to T cells via dendritic cells. This method increased the mobility of Tregs towards the site of abundant α-syn in vitro and in vivo . Consequently, α-syn Tregs showed noteworthy neuroprotective effects against motor function deficits, dopaminergic neuronal loss, and α-syn accumulation in MPTP-induced PD mice. Furthermore, adoptive transfer of α-syn Tregs exerted immunosuppressive effects on activated microglia, especially pro-inflammatory microglia, in PD mice. Our findings suggest that α-syn presentation may provide a significant improvement in neuroprotective activities of Tregs and suggest the effective clinical application of Treg therapy in PD.

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