Li Yuxiao, Wang Tianrong, He Ming, Wang Yu, He Jiayan
Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Department of Otorhinolaryngology, The Seventh Affiliated Hospital Sun-Yat Sen University, Shenzhen, Guangdong, China.
Future Sci OA. 2025 Dec;11(1):2541503. doi: 10.1080/20565623.2025.2541503. Epub 2025 Aug 1.
To investigate the action mechanism of GATA3 and Runt-related transcription factor 1(RUNX1) in modulating regulatory the Th1/Th2 cell differentiation and treat allergic rhinitis (AR).
Established AR model mice by ovalbumin (OVA) and isolated the peripheral blood monocytes (PBMCs), evaluating behavioral changes of AR mice. Analysis of histopathological characteristics by HE. sIgE, IL-4, and IFN-γ were detected by ELISA. RT-qPCR and Western blot detected the expression of GATA3, T-bet, and RUNX1. Using immunofluorescence to detect the expression of GATA and T-bet.
Knockout GATA3 suppressed the expression of GATA3 and concentration of sIgE and IL-4, and promoted the expression of T-bet and concentration of IFN-γ. Knockout GATA3 alleviates inflammation in AR mice by increasing the CD4 IFN-γ cell rate and decreasing the CD4 IL-4 cell rate. RUNX1 and GATA3 were both expressed in the nucleus, GATA3 could bind and interact with RUNX1, si-RUNX1 reversed the effect of sh-GATA3, RUNX1 regulated the balance of Th1/Th2 to alleviate inflammation in AR mice by down-regulating expression of GATA3.
GATA3 regulated the balance of Th1/Th2 cells maybe by the interaction between RUNX1 to improve anti-allergic and anti-inflammatory potential strategies in AR therapy.
探讨GATA3和 runt相关转录因子1(RUNX1)在调节Th1/Th2细胞分化及治疗变应性鼻炎(AR)中的作用机制。
用卵清蛋白(OVA)建立AR模型小鼠,分离外周血单核细胞(PBMCs),评估AR小鼠的行为变化。通过苏木精-伊红(HE)染色分析组织病理学特征。采用酶联免疫吸附测定(ELISA)法检测血清特异性免疫球蛋白E(sIgE)、白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)。采用逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法检测GATA3、T-盒转录因子(T-bet)和RUNX1的表达。用免疫荧光法检测GATA和T-bet的表达。
敲除GATA3可抑制GATA3的表达及sIgE和IL-4的浓度,并促进T-bet的表达及IFN-γ的浓度。敲除GATA3可通过提高CD4 IFN-γ细胞率和降低CD4 IL-4细胞率减轻AR小鼠的炎症。RUNX1和GATA3均在细胞核中表达,GATA3可与RUNX1结合并相互作用,小干扰RNA(si)-RUNX1可逆转短发夹RNA(sh)-GATA3的作用,RUNX1通过下调GATA3的表达调节Th1/Th2平衡以减轻AR小鼠的炎症。
GATA3可能通过与RUNX1相互作用调节Th1/Th2细胞平衡,从而为AR治疗提供改善抗过敏和抗炎潜力的策略。