Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2023 Oct 16;24(20):15237. doi: 10.3390/ijms242015237.
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 ( < 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 ( < 0.05, < 0.01; α-syn Tregs versus poly Tregs), dopaminergic neuronal loss ( < 0.001; α-syn Tregs versus poly Tregs), and α-syn accumulation ( < 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.
帕金森病（PD）是一种长期的神经退行性疾病，其特征是多巴胺能神经元丧失和脑内α-突触核蛋白（α-syn）的聚集。使用调节性 T 细胞（Tregs）的细胞疗法在 PD 小鼠模型中具有治疗进展的潜力；然而，其应用存在一些挑战。在这里，我们提出了一种针对α-syn 的 Treg 特异性扩增（α-syn Treg）策略。我们通过树突状细胞将α-syn 呈递给 T 细胞。这种方法增加了 Tregs 向体外（<0.01；α-syn Tregs 与多克隆 Tregs（多 Tregs））和体内富含α-syn 的部位迁移的能力。因此，α-syn Tregs 对运动功能缺陷（<0.05，<0.01；α-syn Tregs 与多 Tregs）、多巴胺能神经元丧失（<0.001；α-syn Tregs 与多 Tregs）和α-syn 积累（<0.05；α-syn Tregs 与多 Tregs）具有显著的神经保护作用，在 MPTP 诱导的 PD 小鼠中。此外，α-syn Tregs 的过继转移对 PD 小鼠中活化的小胶质细胞（尤其是促炎小胶质细胞）具有免疫抑制作用。我们的研究结果表明，α-syn 的呈递可能显著提高 Treg 的神经保护活性，并提示 Treg 疗法在 PD 中的有效临床应用。
