miR-146a 通过靶向 STAT5b 增强变应性鼻炎中调节性 T 细胞的分化和功能。
miR-146a enhances regulatory T-cell differentiation and function in allergic rhinitis by targeting STAT5b.
机构信息
Department of Otolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.
Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
出版信息
Allergy. 2022 Feb;77(2):550-558. doi: 10.1111/all.15163. Epub 2021 Nov 6.
BACKGROUND
MicroRNA (miR)-146a, as an important immune regulatory factor with an anti-inflammatory effect, plays a crucial role in regulatory T-cell (Tregs) differentiation and function in allergic rhinitis (AR). The present study aimed to investigate the regulatory mechanism employed by miR-146a to control Treg differentiation and function in AR.
METHODS
Expression of miR-146a and STAT5b in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from patients with AR was detected by qPCR and Western blotting. Tregs were quantified by flow cytometry in miR-146a knockdown or STAT5b knockdown PBMCs. FOXP3, IL-10, and TGF-β levels were detected by Western blotting or ELISA in miR-146a knockdown or STAT5b overexpressing PBMCs, as well as in STAT5b knockdown PBMCs overexpressing miR-146a. The effect of miR-146a on STAT5b was observed by luciferase assay and knockdown experiments.
RESULTS
Levels of miR146a and STAT5b in the nasal mucosa or PBMCs were significantly lower in the AR group than in the control group. There were significantly fewer Tregs in miR-146a knockdown or STAT5b knockdown PBMCs compared to control PBMCs. Expression of FOXP3, IL-10, and TGF-β was decreased in the miR-146a knockdown group but increased in the STAT5b overexpression group. In contrast, miR-146a overexpression increased the levels of these factors, but knockdown of STAT5b significantly inhibited this effect. Luciferase assay and knockdown experiments showed that miR-146a bound directly to STAT5b.
CONCLUSIONS
miR-146a enhances Treg differentiation and function in AR by positively targeting STAT5b.
背景
微小 RNA（miR）-146a 作为一种具有抗炎作用的重要免疫调节因子，在调节性 T 细胞（Tregs）分化和功能中发挥着关键作用，在变应性鼻炎（AR）中。本研究旨在探讨 miR-146a 调控 Treg 分化和功能的机制在 AR 中。
方法
通过 qPCR 和 Western blot 检测 AR 患者外周血单个核细胞（PBMC）和鼻黏膜中 miR-146a 和 STAT5b 的表达。通过流式细胞术检测 miR-146a 敲低或 STAT5b 敲低 PBMC 中的 Tregs。通过 Western blot 或 ELISA 检测 miR-146a 敲低或 STAT5b 过表达 PBMC 以及 STAT5b 敲低 PBMC 中转录因子 FOXP3、IL-10 和 TGF-β 的水平。通过荧光素酶测定和敲低实验观察 miR-146a 对 STAT5b 的影响。
结果
与对照组相比，AR 组鼻黏膜或 PBMC 中 miR146a 和 STAT5b 的水平明显降低。与对照组 PBMC 相比，miR-146a 敲低或 STAT5b 敲低 PBMC 中的 Tregs 明显减少。miR-146a 敲低组 FOXP3、IL-10 和 TGF-β 的表达降低，但 STAT5b 过表达组表达增加。相反，miR-146a 过表达增加了这些因子的水平，但 STAT5b 的敲低显著抑制了这种作用。荧光素酶测定和敲低实验表明，miR-146a 直接与 STAT5b 结合。
结论
miR-146a 通过正向靶向 STAT5b 增强 AR 中 Treg 的分化和功能。
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