UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
School of Medicine, Universidad San Francisco de Quito, Quito, Ecuador.
Front Immunol. 2022 Aug 8;13:890781. doi: 10.3389/fimmu.2022.890781. eCollection 2022.
Foxa2, a member of the Forkhead box (Fox) family of transcription factors, plays an important role in the regulation of lung function and lung tissue homeostasis. FOXA2 expression is reduced in the lung and airways epithelium of asthmatic patients and in mice absence of Foxa2 from the lung epithelium contributes to airway inflammation and goblet cell hyperplasia. Here we demonstrate a novel role for Foxa2 in the regulation of T helper differentiation and investigate its impact on lung inflammation. Conditional deletion of from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression . Induction of mouse allergic airway inflammation resulted in more severe disease in the conditional Foxa2 knockout than in control mice, with increased cellular infiltration to the lung, characterized by the recruitment of eosinophils and basophils, increased mucus production and increased production of Th2 cytokines and serum IgE. Thus, these experiments suggest that Foxa2 expression in T-cells is required to protect against the Th2 inflammatory response in allergic airway inflammation and that Foxa2 is important in T-cells to maintain the balance of effector cell differentiation and function in the lung.
叉头框蛋白 A2（Foxa2）是叉头框转录因子家族的成员之一，在肺功能和肺组织稳态的调节中发挥着重要作用。哮喘患者的肺部和气道上皮细胞中 Foxa2 的表达减少，而肺部上皮细胞中 Foxa2 的缺失会导致气道炎症和杯状细胞增生。在这里，我们证明了 Foxa2 在调节辅助性 T 细胞分化中的新作用，并研究了其对肺炎症的影响。条件性敲除 T 细胞中的 Foxa2 导致 Th2 细胞因子分泌和分化增加，但 Th1 分化和 IFN-γ表达减少。诱导小鼠变应性气道炎症导致条件性 Foxa2 敲除小鼠比对照小鼠的疾病更严重，肺内细胞浸润增加，表现为嗜酸性粒细胞和嗜碱性粒细胞的募集、粘液产生增加以及 Th2 细胞因子和血清 IgE 产生增加。因此，这些实验表明，Foxa2 在 T 细胞中的表达对于防止变应性气道炎症中的 Th2 炎症反应是必需的，并且 Foxa2 在 T 细胞中对于维持肺中效应细胞分化和功能的平衡是重要的。
