Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells
Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells
复制标题
丹参酮 IIA 通过促进调节性 T 细胞的分化来改善 CNS 自身免疫。
DOI：
10.1007/s13311-019-00789-2
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发表时间：
2020-04-01
影响因子：
5.7
通讯作者：
Yan, Ya-Ping
中科院分区：
文献类型：
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作者：
Gong, Ye;Liu, Yuan-Chu;Yan, Ya-Ping
Tanshinone IIA（TSA）是一种重要的天然亲脂二萜，来自传统的中国草药Miltiorrhizabunge，由于其抗炎活性，长期以来一直广泛用于预防和治疗各种疾病；但是，抗炎机制仍然未知。在目前的工作中，我们检查了TSA对实验性自身免疫性脑脊髓炎（EAE）的影响，这是一种自动反应性T/B细胞介导的中枢神经系统（CNS）自身免疫模型。 The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease.In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4(+)T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal绳子和脾脏。我们进一步证实，TSA可以通过靶向树突状细胞（DC）来促进幼稚的CD4（+）T细胞的极化，以驱动转化生长因子β1（TGF-BETA 1）上调，并直接靶向天真的CD4（+）T细胞。最重要的是，我们表明TSA诱导的Treg细胞在与TGF-β1偏度treg细胞体内的水平上表现出有效的抑制活性。综上所述，我们的数据提供了证据表明TSA可以促进TREG细胞分化，而TSA可能具有有希望的治疗神经炎性疾病的治疗剂。
Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herbSalvia miltiorrhizaBunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease.In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4(+)T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naive CD4(+)T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factor beta 1 (TGF-beta 1) upregulation and by directly targeting naive CD4(+)T cellsin vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-beta 1-polarized Treg Cellsin vitroandin vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.