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

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 regu...

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Main Authors: Aijun Jia, Yueling Wang, Wenjin Sun, Bing Xiao, Yan Wei, Lulu Qiu, Lin Mu, Li Xu, Jianmin Li, Xiufeng Zhang, Da Liu, Cong Peng, Dongshan Zhang, Xudong Xiang
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2017/6249685
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author Aijun Jia
Yueling Wang
Wenjin Sun
Bing Xiao
Yan Wei
Lulu Qiu
Lin Mu
Li Xu
Jianmin Li
Xiufeng Zhang
Da Liu
Cong Peng
Dongshan Zhang
Xudong Xiang
author_facet Aijun Jia
Yueling Wang
Wenjin Sun
Bing Xiao
Yan Wei
Lulu Qiu
Lin Mu
Li Xu
Jianmin Li
Xiufeng Zhang
Da Liu
Cong Peng
Dongshan Zhang
Xudong Xiang
author_sort Aijun Jia
collection DOAJ
description 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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institution Kabale University
issn 0962-9351
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language English
publishDate 2017-01-01
publisher Wiley
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series Mediators of Inflammation
spelling doaj-art-93d5f484fb2e478f8acf07fd933903ab2025-02-03T06:48:16ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/62496856249685MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 ExpressionAijun Jia0Yueling Wang1Wenjin Sun2Bing Xiao3Yan Wei4Lulu Qiu5Lin Mu6Li Xu7Jianmin Li8Xiufeng Zhang9Da Liu10Cong Peng11Dongshan Zhang12Xudong Xiang13Department 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, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, ChinaDepartment 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, ChinaDepartment of Emergency, Institute of Emergency Medicine and Difficult Diseases, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Respiratory Medicine, The First Hospital of Guangyuan City, 490 Juguo Road, Guangyuan, Sichuan 628000, ChinaDepartment 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, ChinaDepartment of Respiratory Medicine, Peace Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, ChinaDepartment of the Second Thoracic Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, Hunan 410006, ChinaDepartment of Respiratory Medicine, Hunan Provincial People’s Hospital, 61 West Jiefang Road, Changsha, Hunan 410005, ChinaDepartment of Respiratory Medicine, The Second Hospital, University of South China, 30 Jiefang Road, Hengyang, Hunan 421001, ChinaDepartment of Respiratory Medicine, Changsha Central Hospital, 161 South Shaoshan Road, Changsha, Hunan 410004, ChinaDepartment of Dermatology and Venereology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, ChinaDepartment of Emergency, Institute of Emergency Medicine and Difficult Diseases, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Emergency, Institute of Emergency Medicine and Difficult Diseases, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, ChinaTh17 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.http://dx.doi.org/10.1155/2017/6249685
spellingShingle Aijun Jia
Yueling Wang
Wenjin Sun
Bing Xiao
Yan Wei
Lulu Qiu
Lin Mu
Li Xu
Jianmin Li
Xiufeng Zhang
Da Liu
Cong Peng
Dongshan Zhang
Xudong Xiang
MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
Mediators of Inflammation
title MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
title_full MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
title_fullStr MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
title_full_unstemmed MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
title_short MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
title_sort mbd2 regulates th17 cell differentiation and experimental severe asthma by affecting irf4 expression
url http://dx.doi.org/10.1155/2017/6249685
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