Title |
MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α
|
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Published in |
Journal of Inflammation, August 2018
|
DOI | 10.1186/s12950-018-0191-x |
Pubmed ID | |
Authors |
Li Xu, Wen J. Sun, Ai J. Jia, Lu L. Qiu, Bing Xiao, Lin Mu, Jian M. Li, Xiu F. Zhang, Yan Wei, Cong Peng, Dong S. Zhang, Xu D. Xiang |
Abstract |
T helper 17 (Th17) cells have proven to be crucial in the pathogenesis of neutrophils-dominant asthma. Hypoxia inducible factor-1α (HIF-1α) is involved in allergic responses in asthma. Our previous studies indicated that Methtyl-CpG binding domain protein 2 (MBD2) expression was increased in asthma patients. The aim of the present study is to understand how MBD2 interacts with HIF-1α to regulate Th17 cell differentiation and IL-17 expression in neutrophils-dominant asthma. A neutrophils-dominant asthma mouse model was established using female C57BL/6 mice to investigate Th17 cell differentiation and MBD2 and HIF-1α expression regulation using flow cytometry, western blot or qRT-PCR. MBD2 and HIF-1α genes were silenced or overexpressed through lentiviral transduction to explore the roles of MBD2 in Th17 cell differentiation and IL-17 release in neutrophils-dominant asthma. A neutrophilic inflammatory asthma phenotype model was established successfully. This was characterized by airway hyperresponsiveness (AHR), increased BALF neutrophil granulocytes, activated Th17 cell differentiation, and high IL-17 levels. MBD2 and HIF-1α expression were significantly increased in the lung and spleen cells of mice with neutrophils-dominant asthma. Through overexpression or silencing of MBD2 and HIF-1α genes, we have concluded that MBD2 and HIF-1α regulate Th17 cell differentiation and IL-17 secretion. Moreover, MBD2 was also found to regulate HIF-1α expression. Our findings have uncovered new roles for MBD2 and HIF-1α, and provide novel insights into the epigenetic regulation of neutrophils-dominant asthma. |
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United Kingdom | 1 | 50% |
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Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
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Unknown | 27 | 100% |
Demographic breakdown
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Researcher | 5 | 19% |
Student > Bachelor | 4 | 15% |
Student > Master | 3 | 11% |
Student > Postgraduate | 2 | 7% |
Lecturer | 1 | 4% |
Other | 4 | 15% |
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Medicine and Dentistry | 2 | 7% |
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Environmental Science | 1 | 4% |
Other | 2 | 7% |
Unknown | 10 | 37% |