METTL3 mediates SOX5 m6A methylation in bronchial epithelial cells to attenuate Th2 cell differentiation in T2 asthma

作者：Zhifeng Chen, Yulin Shang, Xiufeng Zhang, Wentao Duan, Jianmin Li, Liming Zhu, Libing Ma, Xudong Xiang, Jingsi Jia, Xiaoying Ji, Subo Gong · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e28884 · 被引用次数：11 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Pneumocystis jirovecii pneumonia detection and treatment

Objective: Asthma, a chronic inflammatory disease in which type 2 T helper cells (Th2) play a causative role in the development of T2 asthma. N6-methyladenosine (m6A) modification, an mRNA modification, and methyltransferase-like 3 (METTL3) is involved in the development of T2 asthma by inhibiting Th2 cell differentiation. Sex determining region Y-box protein 5 (SOX5) is involved in regulating T cell differentiation, but its role in T2 asthma was unclear. The objective of this study was to explore the role of METTL3 and SOX5 in T2 asthma and whether there is an interaction between the two. Materials and methods: Adults diagnosed with T2 asthma (n = 14) underwent clinical information collection and pulmonary function tests. In vivo and in vitro T2 asthma models were established using female C57BL/6 mice and human bronchial epithelial cells (HBE). The expressions of METTL3 and SOX5 were detected by Western blot and qRT-PCR and Western blot. Th2 cell differentiation was determined by flow cytometry and IL-4 level was detected by ELISA. m6A methylation level was determined by m6A quantitative assay. The relationship between METTL3 expression and clinical parameters was determined by Spearman rank correlation analysis. The function of METTL3 and SOX5 genes in asthma was investigated in vitro and in vivo. The RNA immunoprecipitation assay detected the specific interaction between METTL3 and SOX5. Results: Patients with T2 asthma displayed lower METTL3 levels compared to healthy con...