C-C趋化因子配体5通过诱导帕金森病模型小鼠外周Th17细胞比例增加、Treg细胞比例减少及促进Th17细胞表达淋巴细胞功能相关抗原1而加重神经炎症的研究  被引量:4

C-C chemokine ligand 5 aggravates neuroinflammation by inducing an increase in the proportion of Th17 cells and a decrease in the proportion of Treg cells,and promoting the expression of lymphocyte functionrelated antigen 1 in Th17 cells on Parkinson’s disease model mice Z

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作  者:赵经纬 薛峥 李静怡 屈艺 王丹蕾 李江婷 安珂 毛志娟 ZHAO Jing-wei;XUE Zheng;LI Jing-yi(Department of Neurology,Tongji Hospital,Tongji Medical College of HUST,Wuhan 430030,China)

机构地区:[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030

出  处:《临床神经病学杂志》2023年第2期134-141,共8页Journal of Clinical Neurology

基  金:国家自然科学基金资助项目(81771376,91849121,8190052652,81901303)。

摘  要:目的探讨帕金森病(PD)中C-C趋化因子配体5(CCL5)对外周CD4^(+)T细胞激活与分化的影响,以及CCL5对Th17细胞与Treg细胞向黑质(SN)迁移介导神经免疫炎症的影响。方法C57B6/J小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)构建PD动物模型,并进行CCL5腹腔注射干预。利用转棒实验和爬杆实验检测小鼠行为能力,利用流式细胞染色检测小鼠外周CD4^(+)T细胞比例及相关表型,利用Western blotting法检测小鼠SN中酪氨酸羟化酶(TH)和α-突触核蛋白的表达,利用免疫荧光染色检测小鼠SN中多巴胺能(DA)神经元数量和Th17/Treg细胞的浸润数量。结果MPTP小鼠与对照组小鼠相比运动功能显著降低,而干预CCL5进一步加重MPTP小鼠的运动功能障碍。MPTP小鼠较对照组小鼠表现为外周Th17细胞比例增加而Treg细胞比例减少;而CCL5干预不仅诱导MPTP小鼠外周Th17细胞比例进一步增加和Treg细胞比例进一步减少,还能够增加淋巴细胞功能相关抗原1(LFA-1)在Th17细胞上的表达但不影响其在Treg细胞中的表达。在中枢,MPTP小鼠SN中DA神经元数量减少、Th17细胞浸润数量增加而Treg细胞浸润数量减少;MPTP小鼠经CCL5干预后,SN中DA神经元数量进一步减少、Th17细胞浸润数量显著增加和Treg细胞浸润数量显著减少。结论CCL5能够诱导MPTP小鼠外周Th17细胞比例增加和Treg细胞比例减少以及诱导Th17细胞表达LFA-1,导致MPTP小鼠SN中Th17细胞数量增加而Treg细胞数量减少,从而加重中枢神经炎症和DA神经元损伤。Objective To investigate the effect of C-C chemokine ligand 5(CCL5)on activation and differentiation of peripheral CD4^(+)T cells in Parkinson’s disease(PD),and the effect of CCL5 on neuroimmune inflammation mediated by the migration of Th17 cells and Treg cells to the substantia nigra(SN).Methods C57B6/J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)to construct an animal model of PD,and CCL5 intraperitoneal injection was carried out.Mice behavior was detected by rotary rod test and pole climbing test.Different proportions of CD4^(+)T cell subsets were detected by flow cytometry staining,and the expression of tyrosine hydroxylase(TH)andα-synuclein in SN was detected by Western blotting.The number of dopaminergic(DA)neurons and the number of infiltration of Th17/Treg cells in SN were detected by immunofluorescence.Results Compared with the control group of mice,MPTP mice showed behavioral deficits,and CCL5 further aggravated behavioral deficits in MPTP mice.Compared with the control group,MPTP mice showed an increased proportion of Th17 cells and a decrease in the proportion of Treg cells in the peripheral blood.However,the CCL5 not only induced a further increase in the proportion of Th17 cells and a further decrease in the proportion of Treg cells in MPTP mice in the peripheral blood,but also increased the expression of lymphocyte function-related antigen 1(LFA-1)on Th17 cells but did not affect its expression on Treg cells.What’s more,the number of DA neurons decreased,the number of Th17 cell infiltrates increased,and the number of Treg cell infiltrates decreased in MPTP mice SN.After CCL5 injection,the number of DA neurons in SN was further reduced,the number of Th17 cell infiltrates increased significantly,and the number of Treg cell infiltrations in MPTP mice was significantly reduced.Conclusion CCL5 can induce an increase in the proportion of Th17 cells and a decrease in the proportion of Treg cells in MPTP mice in the peripheral blood,and induce Th17 cell

关 键 词:帕金森病 TH17细胞 Treg细胞 C-C趋化因子配体5 淋巴细胞功能相关抗原1 

分 类 号:R742.5[医药卫生—神经病学与精神病学]

 

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