MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression.

MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression.
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MBD2 通过影响 IRF4 表达来调节 Th17 细胞分化和实验性严重哮喘

DOI:
10.1155/2017/6249685
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发表时间:
2017
影响因子:
4.6
通讯作者:
Xiang X
Xiang X
中科院分区:
医学3区
文献类型:
--
作者:
Jia A;Wang Y;Sun W;Xiao B;Wei Y;Qiu L;Mu L;Xu L;Li J;Zhang X;Liu D;Peng C;Zhang D;Xiang X

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Th 17细胞和IL-17参与了重症哮喘气道中性粒细胞浸润的特点。哮喘患者外周血CD 4 + T细胞甲基化CpG结合域蛋白2(MBD 2)表达增加。然而,MBD 2在实验性重症哮喘的免疫发病机制和CD 4 + T细胞分化中的表观遗传调控知之甚少。在此,我们建立了嗜中性粒细胞为主的重度哮喘模型,其特征在于气道高反应性(AHR),BALF中性粒细胞(NEU)增加,NEU和IL-17蛋白水平升高,以及更多的Th 17细胞分化。在该模型中,肺和脾细胞中MBD 2和IRF 4蛋白表达增加。在MBD 2和IRF 4基因过表达或沉默的情况下,Th 17细胞的分化和IL-17的分泌显示出积极的变化。IRF 4蛋白表达随MBD 2基因的过表达或沉默而显示出正性变化,而在IRF 4基因的过表达或沉默下MBD 2的表达没有显著差异。这些数据为严重哮喘的表观遗传调控提供了新的见解。
Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4+ T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4+ T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. Under overexpression or silencing of the MBD2 and IRF4 gene, the differentiation of Th17 cells and IL-17 secretion showed positive changes. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was no significant difference in the expression of MBD2 under overexpression or silencing of the IRF4 gene. These data provide novel insights into epigenetic regulation of severe asthma.
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