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

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机构: [1]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 [2]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 [3]Department of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China [4]Department of Respiratory Medicine, The First Hospital of Guangyuan City, 490 Juguo Road, Guangyuan, Sichuan 628000, China [5]Department of Respiratory Medicine, Peace Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, China [6]Department of the Second Thoracic Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, Hunan 410006, China [7]Department of Respiratory Medicine, Hunan Provincial People’s Hospital, 61 West Jiefang Road, Changsha, Hunan 410005, China [8]Department of Respiratory Medicine, The Second Hospital, University of South China, 30 Jiefang Road, Hengyang, Hunan 421001, China [9]Department of Respiratory Medicine, Changsha Central Hospital, 161 South Shaoshan Road, Changsha, Hunan 410004, China [10]Department of Dermatology and Venereology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
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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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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 免疫学 4 区 细胞生物学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 细胞生物学 3 区 免疫学
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第一作者机构: [1]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 [2]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
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