The therapeutic effect of gold clusters in an EAE model of multiple sclerosis by regulating T cell differentiation
The therapeutic effect of gold clusters in an EAE model of multiple sclerosis by regulating T cell differentiation
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DOI：
10.1016/j.nantod.2023.102128
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发表时间：
2024-02
期刊：
影响因子：
17.4
通讯作者：
Zhesheng He;Jing Lai;Huangwei Wang;Yating He;Chunyu Zhang;Liang Gao;Huan Huang;Lirong Zheng;Junwei Hao;Xueyun Gao;Fuping Gao
中科院分区：
文献类型：
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作者：
Zhesheng He;Jing Lai;Huangwei Wang;Yating He;Chunyu Zhang;Liang Gao;Huan Huang;Lirong Zheng;Junwei Hao;Xueyun Gao;Fuping Gao
多发性硬化症 (MS) 是由中枢神经系统 (CNS) 异常的自身免疫反应引起的，导致进行性脱髓鞘。目前的疗法主要是疾病缓解疗法，由于成本较高、患者依从性低和严重的副作用，其广泛使用受到限制。在这里，我们首先证明，在多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，纳米金簇（GA，分子式Au29SG27）在预防或治疗时可以显着减轻或逆转临床症状并预防神经元脱髓鞘。 GA 减少中枢神经系统中 Th1 和 Th17 细胞的浸润以及相关促炎细胞因子的分泌。值得注意的是，GA 在体外对 CD4+T 细胞分化为 Th1 和 Th 17 具有有效的直接抑制活性，但对 T 细胞的凋亡和激活没有影响。机制研究表明，GA 通过与细胞中的 JAK 蛋白特异性 Au 结合来抑制 JAK/STAT 信号传导，这对于 Th 细胞分化至关重要。总的来说，我们的结果揭示了 GA 作为一种低毒高效的 MS 治疗新型纳米药物。
Multiple sclerosis (MS) is caused by an aberrant autoimmune response in the central nervous system (CNS), which results in progressive demyelination. Current therapies, mostly disease-modifying therapies, have limited wide use due to their higher costs, low patient's compliance, and serious side effects. Here, we firstly show that nano-sized gold clusters (GA, molecular formula Au29SG27) can significantly attenuate or reverse clinical symptoms and prevent neuronal demyelination in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS when administered prophylactically or therapeutically. GA reduces the infiltration of Th1 and Th17 cells, and the secretion of associated pro-inflammatory cytokines in the CNS. Notably, GA shows potent direct inhibitory activity on the differentiation of CD4+T cells into Th1 and Th 17 in vitro with no effect on apoptosis and activation of T cells. Mechanistic studies show that GA inhibit JAK/STAT signaling, which is critical for Th-cell differentiation, through specific Au-binding with JAK protein in cells. Collectively, our results sheds light on GA as a novel nano-drug for MS treatment with low toxicity and high efficiency.