BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS Our findings have uncovered new roles for MBD2 and HIF-1α, and provide novel insights into the epigenetic regulation of neutrophils-dominant asthma.

中文翻译：

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MBD2 通过 HIF-1α 调节中性粒细胞显性哮喘中 Th17 细胞的分化和功能。

背景 T 辅助 17 (Th17) 细胞已被证明在嗜中性粒细胞为主的哮喘的发病机制中至关重要。缺氧诱导因子-1α (HIF-1α) 参与哮喘的过敏反应。我们之前的研究表明，哮喘患者中甲基-CpG 结合域蛋白 2 (MBD2) 的表达增加。本研究的目的是了解 MBD2 如何与 HIF-1α 相互作用以调节中性粒细胞为主的哮喘中的 Th17 细胞分化和 IL-17 表达。方法采用雌性C57BL/6小鼠建立中性粒细胞为主的哮喘小鼠模型，采用流式细胞术、western blot或qRT-PCR研究Th17细胞分化及MBD2和HIF-1α表达调控。MBD2和HIF-1α基因通过慢病毒转导沉默或过表达，以探索MBD2在Th17细胞分化和IL-17释放中性粒细胞为主的哮喘中的作用。结果成功建立中性粒细胞炎症性哮喘表型模型。这以气道高反应性 (AHR)、BALF 中性粒细胞增加、激活的 Th17 细胞分化和高 IL-17 水平为特征。MBD2和HIF-1α在中性粒细胞为主的哮喘小鼠肺和脾细胞中的表达显着增加。通过 MBD2 和 HIF-1α 基因的过表达或沉默，我们得出结论 MBD2 和 HIF-1α 调节 Th17 细胞分化和 IL-17 分泌。此外，还发现 MBD2 调节 HIF-1α 表达。结论 我们的研究结果揭示了 MBD2 和 HIF-1α 的新作用，