Combination of androgen and estrogen improves asthma by mediating Runx3 expression

作者：Yi He, Binaya Wasti, Yu Yuan, Zhifeng Chen, Wentao Duan, Jingsi Jia, Bing Xiao, Xiufeng Zhang, Jianmin Li, Qingping Zeng, Ma Libing, Shaokun Liu, Xudong Xiang · 发表于：International Journal of Medical Sciences · 年份：2024 · DOI：10.7150/ijms.91253 · 被引用次数：8 · 研究领域：Asthma and respiratory diseases、IL-33, ST2, and ILC Pathways

Objective: Asthma is a chronic heterogeneous airway disease, and imbalanced T-helper type 1 (Th1) and Th2 cell-mediated inflammation contribute to its pathogenesis. Although it has been suggested that androgen and estrogen were involved in development of asthma, the underlying mechanisms remained largely unclear. Studies have demonstrated that Runx3 could promote naive CD4 + T cells to differentiate into Th1 cells. Hence, our study aimed to explore the potential regulatory mechanism of androgen and estrogen on asthma via modulating Runx3. Methods: First, clinical assessments and pulmonary function tests were conducted on 35 asthma patients and 24 healthy controls. The concentrations of androgen, estrogen, and androgen estrogen ratios were assessed in peripheral blood samples of asthma patients and healthy controls. Then, a murine asthma model was established to explore the effects of estrogen and androgen (alone or in combination) on asthma. Third, an in vitro assay was used to explore the mechanism of combination of androgen and estrogen in asthma. Results: We observed decreased androgen and increased estrogen levels in asthma patients compared with healthy controls. In mice with experimental asthma, there were increased serum concentrations of estrogen and decreased serum concentrations of androgen, intervention with combination of androgen and estrogen alleviated airway inflammations, increased Runx3 expressions and elevated Th1 differentiation. In CD4+ T cells co-cultured...