IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages
IL-33 attenuates EAE by suppressing IL-17 and IFN-γ production and inducing alternatively activated macrophages
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DOI：
10.1002/eji.201141947
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发表时间：
2012-07-01
影响因子：
5.4
通讯作者：
Liew, Foo Y.
中科院分区：
文献类型：
--
作者：
Jiang, Hui-Rong;Milovanovic, Marija;Liew, Foo Y.
白细胞介素（IL）-33是IL-1细胞因子家族的成员，是与多种免疫介导的疾病相关的免疫系统的重要调节剂。中枢神经系统（CNS）表达高水平的IL-33，表明IL-33在自身免疫性CNS疾病中的潜在作用。我们研究了IL-33在实验性自身免疫性脑脊髓炎（EAE）小鼠发病过程中的表达和作用。我们在这里报告IL-33及其受体ST 2（IL-33 Ra）在脊髓组织中高度表达，ST 2在EAE小鼠脊髓中的表达显著增加。此外，与野生型（WT）小鼠相比，ST 2缺陷型（ST 2-/-）小鼠发展加重的EAE，而用IL-33治疗的WT而非ST 2-/- EAE小鼠发展显著减弱的疾病。IL-33治疗的小鼠IL-17和IFN-？但产生了增加量的IL-5和IL-13。IL-33处理小鼠的淋巴结和脾巨噬细胞显示出向交替活化的巨噬细胞（M2）表型的极化，MR+PD-L2+细胞的频率显著增加。重要的是，这些IL-33处理的巨噬细胞的过继转移减弱了EAE的发展。因此，我们的数据表明，IL-33在自身免疫性中枢神经系统疾病中发挥治疗作用，主要是通过将致病性Th 17/Th 1应答转换为Th 2活性，以及通过抗炎M2巨噬细胞的极化。
Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Ra) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2-/-) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2-/- EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-? but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR+PD-L2+ cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.