■帕金森病(PD),这与自身免疫性疾病有关,其特征在于α-突触核蛋白(α-Syn)的病理沉积和多巴胺能(DA)神经元的损失。Th17细胞被认为是DA神经元直接损失的原因。C-C趋化因子配体5(CCL5)特异性诱导Th17细胞浸润到SN中。然而,CCL5对PD中Th17细胞的特异性作用以及CCL5与Th17细胞中淋巴细胞功能相关抗原-1(LFA-1)表达之间的关系尚不清楚。
我们评估了CCL5对用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)处理的小鼠中Th17细胞中LFA-1表达的影响,并在体外检测了CCL5刺激下Th17细胞分化。此外,我们在体内和体外评估了CCL5对CCL5刺激的Th17细胞中酪氨酸激酶ζ链相关蛋白激酶70(ZAP70)和淋巴细胞特异性蛋白酪氨酸激酶(LCK)活性的影响.
■CCL5在MPTP处理的小鼠中增加了外周Th17细胞的比例,LFA-1在Th17细胞上的表达,和MPTP处理的小鼠的SN中的Th17细胞水平。CCL5在体外促进幼稚T细胞中Th17细胞分化和LFA-1表达。此外,CCL5通过刺激幼稚CD4+T细胞中的LCK和ZAP70活化来增加Th17细胞分化和LFA-1表达。抑制LCK和ZAP70活化可降低MPTP处理小鼠外周血Th17细胞比例和LFA-1表面表达,SN中Th17细胞水平也显著降低。
■CCL5通过激活LCK和ZAP70增加Th17细胞分化和LFA-1蛋白表达,可以增加SN中Th17细胞的数量,诱导DA神经元死亡并加重PD。
UNASSIGNED: Parkinson\'s disease (PD), which is associated to autoimmune disorders, is characterized by the pathological deposition of alpha-synuclein (α-Syn) and loss of dopaminergic (DA) neurons. Th17 cells are thought to be responsible for the direct loss of DA neurons. C-C chemokine ligand 5 (CCL5) specifically induces Th17 cell infiltration into the SN. However, the specific effect of CCL5 on Th17 cells in PD and the relationship between CCL5 and lymphocyte function-associated antigen-1 (LFA-1) expression in Th17 cells are unknown.
UNASSIGNED: We evaluated the effects of CCL5 on LFA-1 expression in Th17 cells in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined Th17 cell differentiation upon CCL5 stimulation in vitro. Furthermore, we assessed the effects of CCL5 on tyrosine kinase zeta-chain-associated protein kinase 70 (ZAP70) and lymphocyte-specific protein tyrosine kinase (LCK) activity in CCL5-stimulated Th17 cells in vivo and in vitro.
UNASSIGNED: CCL5 increased the proportion of peripheral Th17 cells in MPTP-treated mice, LFA-1 expression on Th17 cells, and Th17 cell levels in the SN of MPTP-treated mice. CCL5 promoted Th17 cell differentiation and LFA-1 expression in naive T cells in vitro. Moreover, CCL5 increased Th17 cell differentiation and LFA-1 expression by stimulating LCK and ZAP70 activation in naive CD4+ T cells. Inhibiting LCK and ZAP70 activation reduced the proportion of peripheral Th17 cells and LFA-1 surface expression in MPTP-treated mice, and Th17 cell levels in the SN also significantly decreased.
UNASSIGNED: CCL5, which increased Th17 cell differentiation and LFA-1 protein expression by activating LCK and ZAP70, could increase the Th17 cell number in the SN, induce DA neuron death and aggravate PD.