Astragaloside IV regulates differentiation and induces apoptosis of activated CD4+ T cells in the pathogenesis of experimental autoimmune encephalomyelitis
Astragaloside IV regulates differentiation and induces apoptosis of activated CD4+ T cells in the pathogenesis of experimental autoimmune encephalomyelitis
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黄芪甲苷在实验性自身免疫性脑脊髓炎发病机制中调节活化CD4 T细胞分化并诱导凋亡
DOI：
10.1016/j.taap.2018.10.024
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发表时间：
2019-01-01
影响因子：
3.8
通讯作者：
Wu，Xiaojun
中科院分区：
文献类型：
--
作者：
Yang，Liu;Xing，Faping;Wu，Xiaojun
CD4+T 细胞，特别是辅助性 T 细胞（Th1、Th2 和 Th17）和调节性 T 细胞 (Treg) 在多发性硬化症 (MS) 的发病机制中发挥着关键作用，多发性硬化症是一种发生在中枢神经系统 (CNS) 的脱髓鞘自身免疫性疾病。黄芪甲苷IV（ASI，CAS：84687-43-4）是从黄芪中分离得到的皂苷之一，是一种具有免疫调节作用的中药。迄今为止，ASI对MS动物模型实验性自身免疫性脑脊髓炎（EAE）是否具有疗效、如何影响CD4+T细胞亚群以及潜在机制尚未明确阐明。在本研究中，发现 ASI 在治疗方案中可以有效改善 EAE 的进展并阻止其复发。它通过抑制Th1和Th17细胞的百分比，显着减少EAE小鼠中枢神经系统的脱髓鞘和炎症浸润，这与抑制JAK/STAT和NF-κB信号通路密切相关。 ASI 还增加了脾脏和中枢神经系统中 Treg 细胞的百分比，同时伴随着 Foxp3 的升高。然而，体外实验表明ASI可以调节Th17和Treg细胞的分化，但不能调节Th1细胞。此外，它可能通过调节 STAT3/Bcl-2/Bax 信号通路诱导 MOG 刺激的 CD4+T 细胞凋亡。总之，我们的研究结果表明，ASI 可以调节自身反应性 CD4+T 细胞的分化，是治疗 MS 和其他类似自身免疫性疾病的潜在前药或药物。
CD4+T cells, especially T-helper (Th) cells (Th1, Th2 and Th17) and regulatory T cells (Treg) play pivotal role in the pathogenesis of multiple sclerosis (MS), a demyelinating autoimmune disease occurring in central nervous system (CNS). Astragaloside IV (ASI, CAS: 84687-43-4) is one of the saponins isolated fromAstragalusmembranceus, a traditional Chinese medicine with immunomodulatory effect. So far, whether ASI has curative effect on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and how it affects the subsets of CD4+T cells, as well as the underlying mechanism have not been clearly elucidated. In the present study, ASI was found to ameliorate the progression and hamper the recurrence of EAE effectively in the treatment regimens. It significantly reduced the demyelination and inflammatory infiltration of CNS in EAE mice by suppressing the percentage of Th1 and Th17 cells, which was closely associated with the inhibition of JAK/STAT and NF-κB signaling pathways. ASI also increased the percentage of Treg cells in spleen and CNS, which was accompanied by elevated Foxp3. However,in vitroexperiments disclosed that ASI could regulate the differentiation of Th17 and Treg cells but not Th1 cells. In addition, it induced the apoptosis of MOG-stimulated CD4+T cells probably through modulating STAT3/Bcl-2/Bax signaling pathways. Together, our findings suggested that ASI can modulate the differentiation of autoreactive CD4+T cells and is a potential prodrug or drug for the treatment of MS and other similar autoimmune diseases.