Methyl Butyrate Alleviates Experimental Autoimmune Encephalomyelitis and Regulates the Balance of Effector T Cells and Regulatory T Cells.
Methyl Butyrate Alleviates Experimental Autoimmune Encephalomyelitis and Regulates the Balance of Effector T Cells and Regulatory T Cells.
复制标题
丁酸甲酯缓解实验性自身免疫性脑脊髓炎并调节效应T细胞和调节性T细胞的平衡
DOI：
10.1007/s10753-021-01596-8
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发表时间：
2021
期刊：
影响因子：
5.1
通讯作者：
Du Changsheng
中科院分区：
文献类型：
--
作者：
Wang Chun;Yang Jingshu;Xie Ling;Saimaier Kaidireya;Zhuang Wei;Han Mengyao;Liu Guangyu;Lv Jie;Shi Guangfeng;Li Ning;Du Changsheng
多发性硬化（MS）是中枢神经系统（CNS）的自身免疫性疾病，其特征在于脱髓鞘性神经病。MS的病因尚不清楚，其治疗仍然是一个重大的医学挑战。我们在寻找有效治疗实验性自身免疫性脑脊髓炎（EAE）这一MS动物模型的药物的同时，也希望进一步探讨其可能的发病机制。在本研究中，我们研究了丁酸甲酯（MB）是否可以减轻EAE及其潜在的机制。在EAE小鼠中，我们发现MB给药可有效缓解其临床体征并改善CNS的组织病理学表现。在中枢神经系统和肠固有层，我们观察到较少的效应T细胞，包括Th 1和Th 17，在MB治疗组。MB还增加外周免疫器官中调节性T细胞的比例和IL-10的分泌。在体外，MB导致抑制Th 1细胞和促进调节性T细胞的分化。鉴于MB在体外对Th 17细胞分化没有直接影响，我们假设MB通过抑制IL-6的分泌间接抑制Th 17细胞，这后来在体外和体内都得到了证实。此外，我们发现MB处理上调小鼠Maf基因表达，这解释了其促进IL-10分泌的原因。以上结果提示MB可能为MS发病机制的研究提供新的思路，对新药开发具有积极意义。
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. The etiology of MS is not yet clear and its treatment remains a major medical challenge. While we search for drugs that can effectively treat experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we also hope to further explore its possible pathogenesis. In the present study, we investigated whether methyl butyrate (MB) could alleviate EAE and its potential mechanisms. In EAE mice, we found that administration of MB was effective in alleviating their clinical signs and improving histopathological manifestations of the CNS. In the CNS and intestinal lamina propria, we observed fewer effector T cells, including Th1 and Th17, in the MB-treated group. MB also increased the proportion of regulatory T cells and the secretion of IL-10 in peripheral immune organs. In vitro, MB led to suppression of Th1 cells and promotion of regulatory T cells in their differentiation. Given that MB had no direct effect on Th17 cell differentiation in vitro, we hypothesized that MB suppressed Th17 cells indirectly by inhibiting the secretion of IL-6, which was later confirmed both in vitro and in vivo. In addition, we found that MB treatment upregulatedMafgene expression in mice, which explained its promotion of IL-10 secretion. The above findings suggest that MB may provide new ideas for the study of the mechanism of MS and have positive implications for new drug development.