白细胞介素-2可扩增帕金森病中的神经保护性调节性T细胞。
Interleukin-2 expands neuroprotective regulatory T cells in Parkinson's disease.
作者信息
Markovic Milica, Yeapuri Pravin, Namminga Krista L, Lu Yaman, Saleh Maamoon, Olson Katherine E, Gendelman Howard E, Mosley R Lee
机构信息
Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, 68198 Omaha, NE, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
出版信息
NeuroImmune Pharm Ther. 2022 Jun 21;1(1):43-50. doi: 10.1515/nipt-2022-0001. eCollection 2022 Mar.
BACKGROUND
Pharmacological approaches that boost neuroprotective regulatory T cell (Treg) number and function lead to neuroprotective activities in neurodegenerative disorders.
OBJECTIVES
We investigated whether low-dose interleukin 2 (IL-2) expands Treg populations and protects nigrostriatal dopaminergic neurons in a model of Parkinson's disease (PD).
METHODS
IL-2 at 2.5 × 10 IU/dose/mouse was administered for 5 days. Lymphocytes were isolated and phenotype determined by flow cytometric analyses. To 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, 0.5 × 10 of enriched IL-2-induced Tregs were adoptively transferred to assess the effects on nigrostriatal neuron survival.
RESULTS
IL-2 increased frequencies of CD4CD25CD127FoxP3 Tregs that express ICOS and CD39 in blood and spleen. Adoptive transfer of IL-2-induced Tregs to MPTP-treated recipients increased tyrosine hydroxylase (TH) nigral dopaminergic neuronal bodies by 51% and TH striatal termini by 52% compared to control MPTP-treated animal controls.
CONCLUSIONS
IL-2 expands numbers of neuroprotective Tregs providing a vehicle for neuroprotection of nigrostriatal dopaminergic neurons in a pre-clinical PD model.
背景
增强神经保护性调节性T细胞（Treg）数量和功能的药理学方法可在神经退行性疾病中产生神经保护作用。
目的
我们研究了低剂量白细胞介素2（IL-2）是否能在帕金森病（PD）模型中扩大Treg群体并保护黑质纹状体多巴胺能神经元。
方法
以2.5×10 IU/剂量/小鼠给予IL-2，持续5天。分离淋巴细胞并通过流式细胞术分析确定其表型。将0.5×10的富集IL-2诱导的Tregs过继转移至1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）中毒的小鼠，以评估对黑质纹状体神经元存活的影响。
结果
IL-2增加了血液和脾脏中表达ICOS和CD39的CD4CD25CD127FoxP3 Tregs的频率。与对照MPTP处理的动物对照组相比，将IL-2诱导的Tregs过继转移至MPTP处理的受体后，酪氨酸羟化酶（TH）黑质多巴胺能神经元胞体增加了51%，TH纹状体终末增加了52%。
结论
IL-2可扩大神经保护性Tregs的数量，为临床前PD模型中黑质纹状体多巴胺能神经元的神经保护提供了一种手段。
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