IL-33 blockade suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice
IL-33 blockade suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice
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IL-33 阻断可抑制 C57BL/6 小鼠实验性自身免疫性脑脊髓炎的发展
DOI：
10.1016/j.jneuroim.2012.03.016
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发表时间：
2012-06-15
影响因子：
3.3
通讯作者：
Wang, Yaqing
中科院分区：
文献类型：
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作者：
Li, Mingcai;Li, Yan;Wang, Yaqing
IL-33是最近发现的IL-1家族成员，据报道在几种炎症性疾病中起致病作用。在这项研究中，我们评估了IL-33在多发性硬化症，实验性自身免疫性脑脊髓炎（EAE）小鼠模型中的作用。我们发现在髓鞘少突胶质细胞糖蛋白（MOG）（35-55）肽诱导的EAE中，IL-33及其受体ST2在小鼠脊髓中的表达显著升高。在EAE小鼠诱导期给予阻断性抗il -33抗体可显著抑制EAE的发作和严重程度，并减少MOG（35-55）诱导的ifn - γ和IL-17的产生。相反，重组IL-33治疗与ifn - γ和IL-17诱导增加相关，加重了EAE的病程。此外，抗il -33治疗导致EAE小鼠脊髓IL-17、ifn - γ、t -bet和ROR γ t的表达显著降低，IL-10和tgf - β的表达上调。这些结果表明内源性IL-33在EAE的发病机制中起着关键作用，表明阻断IL-33对EAE具有显著的保护作用。(c) 2012 Elsevier B.V.版权所有
IL-33 is a recently described member of the IL-1 family that has been reported to have a pathogenic role in several inflammatory diseases. In this study, we evaluated the role of IL-33 in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). We showed that the expression of IL-33 and its receptor, ST2, was markedly elevated in the spinal cord of mice during myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide-induced EAE. Administration of a blocking anti-IL-33 antibody in mice of EAE during the induction phase significantly inhibited the onset and severity of EAE and reduced MOG(35-55)-induced IFN-gamma and IL-17 production. In contrast, treatment with recombinant IL-33 worsened the disease course of EAE in association with increased induction of both IFN-gamma and IL-17. Furthermore, anti-IL-33 treatment caused a remarkable decrease in expression of IL-17, IFN-gamma, T-bet and ROR gamma t, and an upregulation of IL-10 and TGF-beta in the spinal cord of EAE mice. These results demonstrate that endogenous IL-33 plays a pivotal role in the pathogenesis of EAE and indicate that blockade of IL-33 has a significant protective effect against EAE. (c) 2012 Elsevier B.V. All rights reserved.