Interleukin-10 plays a crucial role in suppression of experimental autoimmune encephalomyelitis by Bowman-Birk inhibitor.
Interleukin-10 plays a crucial role in suppression of experimental autoimmune encephalomyelitis by Bowman-Birk inhibitor.
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DOI：
10.1016/j.jneuroim.2012.01.005
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发表时间：
2012-04
影响因子：
3.3
通讯作者：
Rostami, Abdolmohamad
中科院分区：
文献类型：
--
作者：
Dai, Hong;Ciric, Bogoljub;Zhang, Guang-Xian;Rostami, Abdolmohamad
Bowman-Birk抑制剂（BBI）是一种大豆衍生的丝氨酸蛋白酶抑制剂，具有抗炎特性。实验性自身免疫性脑脊髓炎（EAE）作为中枢神经系统（CNS）炎症性疾病多发性硬化症（MS）的动物模型。EAE由Th1和Th17细胞介导，Th1和Th17细胞迁移到CNS并引发针对髓鞘组分的炎症，导致CNS病理学和神经学临床缺陷。我们以前已经表明，口服BBI治疗可延迟EAE的发作并降低其严重程度。这些有益效果与BBI处理小鼠的免疫细胞的IL-10分泌增加有关。然而，我们不知道这是一种因果关系还是仅仅是一种附带现象。在本研究中，我们提供的证据表明，BBI调节EAE中的CD4 + T细胞免疫应答。BBI给药以IL-10依赖的方式延迟EAE的发作并降低其严重程度，因为BBI介导的EAE抑制在IL-10敲除小鼠中被消除。有益的效果伴随着IFN-γ、IL-17的减少和IL-10的产生增加，以及Foxp3表达的增加。在BBI治疗期间，外周和CNS中的IL-10的主要来源是CD4 + T细胞。此外，与PBS处理的对照动物相比，BBI处理的小鼠CNS中浸润细胞的数量减少，包括Th17细胞。总之，我们的数据为IL-10在BBI介导的EAE抑制中的重要作用提供了明确的证据，并表明BBI可能是开发新型MS治疗的有希望的候选者。
The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with anti-inflammatory properties. Experimental autoimmune encephalomyelitis (EAE) serves as an animal model of the central nervous system (CNS) inflammatory disorder multiple sclerosis (MS). EAE is mediated by Th1 and Th17 cells which migrate into the CNS and initiate inflammation directed against myelin components, resulting in CNS pathology and neurological clinical deficit. We have shown previously that oral treatment with BBI delays onset of EAE and reduces its severity. These beneficial effects were associated with an increase in IL-10 secretion by immune cells of BBI-treated mice. It is not known, however, whether this was a causal relationship or simply an epiphenomenon. In the present study we provide evidence that BBI regulates CD4+ T cell immune responses in EAE. BBI administration delayed the onset of EAE and reduced its severity in an IL-10-dependent manner, as BBI-mediated suppression of EAE was abrogated in IL-10 knockout mice. The beneficial effects were accompanied by reduced IFN-γ, IL-17 and increased IL-10 production, as well as increased Foxp3 expression. CD4+ T cells were the major source of IL-10 in the periphery and in the CNS during BBI treatment. Furthermore, BBI-treated mice had reduced numbers of infiltrated cells in the CNS, including Th17 cells, as compared with PBS-treated control animals. In conclusion, our data provide clear evidence for the essential role of IL-10 in BBI-mediated suppression in EAE, and indicate that BBI may be a promising candidate for the development of a novel MS therapy.
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DOI：
10.1084/jem.20102010
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cruz-Orengo L;Holman DW;Dorsey D;Zhou L;Zhang P;Wright M;McCandless EE;Patel JR;Luker GD;Littman DR;Russell JH;Klein RS
通讯作者：
Klein RS
影响因子：
4.8
作者：
Daly, Norelle L.;Chen, Yi-Kuang;Craik, David J.
通讯作者：
Craik, David J.
影响因子：
4.4
作者：
Mekala, DJ;Alli, RS;Geiger, TL
通讯作者：
Geiger, TL
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.8
作者：
McGeachy, MJ;Anderton, SM
通讯作者：
Anderton, SM