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

Seon Young Park, Hye Jin Yang, Soyoung Kim, Juwon Yang, Hyemin Go, Hyunsu Bae

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 (α-syn Treg). 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 (p < 0.01; α-syn Tregs versus polyclonal Tregs (poly Tregs)) and in vivo. Consequently, α-syn Tregs showed noteworthy neuroprotective effects against motor function deficits (p < 0.05, p < 0.01; α-syn Tregs versus poly Tregs), dopaminergic neuronal loss (p < 0.001; α-syn Tregs versus poly Tregs), and α-syn accumulation (p < 0.05; α-syn Tregs versus poly Tregs) in MPTP-induced PD mice. Furthermore, the 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.

Original languageEnglish
Article number15237
JournalInternational Journal of Molecular Sciences
Volume24
Issue number20
DOIs
Publication statusPublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Parkinson’s disease
  • alpha-synuclein
  • regulatory T cell

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