Regulatory T cells (Tregs), which secrete transforming growth factor (TGF)-β and interleukin (IL)-10, have essential role in anti-inflammatory and neurotrophic functions. Herein, we explore the neuroprotection of Tregs in Parkinson’s disease (PD) by adoptive transfer of Tregs. Tregs, isolated by magnetic sorting, were activated in vitro and then were adoptively transferred to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated mice. Neuroinflammation, dopaminergic neuronal loss and behavioral changes of PD mice were evaluated. Live cell imaging system detected a dynamic contact of Tregs with MN9D cells that were stained with CD45 and galectin-1, respectively. Tregs prevented MPTP-induced dopaminergic neuronal loss, behavioral changes, and attenuated the inflammatory reaction in the brain. When blockade the LFA-1 activity in Tregs or the ICAM-1 activity in endothelial cells, the percentage of Tregs in substantia nigra (SN) decreased. CD45 and galectin-1 were expressed by Tregs and MN9D cells, respectively. CD45-labeled Tregs dynamically contacted with galectin-1-labeled MN9D cells. Inhibiting CD45 in Tregs impaired the ability of Tregs to protect dopaminergic neurons against MPP⁺ toxicity. Similarly, galectin-1 knockdown in MN9D cells reduced the ability of Tregs neuroprotection. Adoptive transfer of Tregs protects dopaminergic neurons in PD mice by a cell-to-cell contact mechanism underlying CD45-galectin-1 interaction.

Graphical Abstract

中文翻译：

---

Treg细胞可减轻帕金森氏病小鼠模型中的神经炎症并保护神经元。

分泌转化生长因子（TGF）-β和白介素（IL）-10的调节性T细胞（Tregs）在抗炎和神经营养功能中具有重要作用。在本文中，我们通过过继转移Tregs探索帕金森氏病（PD）中Tregs的神经保护作用。通过磁选分离的Treg在体外被激活，然后被过继转移到1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠中。评价PD小鼠的神经炎症，多巴胺能神经元损失和行为改变。活细胞成像系统检测到Treg与MN9D细胞的动态接触，MN9D细胞分别用CD45和Galectin-1染色。Tregs预防了MPTP引起的多巴胺能神经元丢失，行为改变，并减轻了大脑的炎症反应。当阻断Tregs中的LFA-1活性或内皮细胞中的ICAM-1活性时，黑质（SN）中Tregs的百分比降低。Tregs和MN9D细胞分别表达CD45和galectin-1。CD45标记的Tregs与半乳糖凝集素1标记的MN9D细胞动态接触。在Treg中抑制CD45会破坏Treg保护多巴胺能神经元抵抗MPP的能力。⁺毒性。同样，MN9D细胞中的半乳糖凝集素-1敲低降低了Tregs神经保护的能力。Tregs的过继转移通过CD45-galectin-1相互作用下的细胞间接触机制保护PD小鼠中的多巴胺能神经元。

图形概要