Department of Respiratory Medicine, Hunan Centre for Evidence-Based Medicine, Research Unit of Respiratory Diseases, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
Department of Emergency, Institute of Emergency Medicine and Difficult Diseases, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China.
Mediators Inflamm. 2017;2017:6249685. doi: 10.1155/2017/6249685. Epub 2017 Jul 20.
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.
Th17 细胞和 IL-17 参与重症哮喘发病机制中的气道中性粒细胞浸润特征。哮喘患者外周血样本中的 CD4 T 细胞中甲基化 CpG 结合域蛋白 2 (MBD2) 的表达增加。然而，关于 MBD2 在实验性重症哮喘的免疫发病机制和 CD4 T 细胞分化中的表观遗传调控，目前知之甚少。在这里，我们建立了一个以中性粒细胞为主的重症哮喘模型，其特征是气道高反应性（AHR）、BALF 中性粒细胞（NEU）增加、更高的 NEU 和 IL-17 蛋白水平，以及更多的 Th17 细胞分化。在该模型中，MBD2 和 IRF4 蛋白在肺和脾细胞中的表达增加。在 MBD2 和 IRF4 基因的过表达或沉默下，Th17 细胞的分化和 IL-17 的分泌显示出阳性变化。IRF4 蛋白表达随着 MBD2 基因的过表达或沉默而呈阳性变化，而在 IRF4 基因的过表达或沉默下，MBD2 的表达没有显著差异。这些数据为重症哮喘的表观遗传调控提供了新的见解。
