MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1?.

ABSTRACT: T helper 17 (Th17) cells have proven to be crucial in the pathogenesis of neutrophils-dominant asthma. Hypoxia inducible factor-1? (HIF-1?) 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-1? 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-1? expression regulation using flow cytometry, western blot or qRT-PCR. MBD2 and HIF-1? 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-1? expression were significantly increased in the lung and spleen cells of mice with neutrophils-dominant asthma. Through overexpression or silencing of MBD2 and HIF-1? genes, we have concluded that MBD2 and HIF-1? regulate Th17 cell differentiation and IL-17 secretion. Moreover, MBD2 was also found to regulate HIF-1? expression.Our findings have uncovered new roles for MBD2 and HIF-1?, and provide novel insights into the epigenetic regulation of neutrophils-dominant asthma.

SUBMITTER: Xu L 

PROVIDER: S-EPMC6102869 | biostudies-other | 2018

REPOSITORIES: biostudies-other