The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease.
The Pioneer Transcription Factor Foxa2 Modulates T Helper Differentiation to Reduce Mouse Allergic Airway Disease.
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DOI：
10.3389/fimmu.2022.890781
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
Foxa2是叉头框（Fox）转录因子家族的成员，在肺功能调节和肺组织内稳态中起重要作用。哮喘患者的肺和气道上皮中FOXA2表达降低，在肺上皮中缺乏Foxa2的小鼠会出现气道炎症和杯状细胞增生。在此我们展示了Foxa2在调节辅助性T细胞分化中的新作用，并研究了它对肺部炎症的影响。在T细胞中条件性敲除Foxa2会导致体外Th2细胞因子分泌和分化增加，但Th1分化和干扰素 - γ表达降低。诱导小鼠过敏性气道炎症后，条件性Foxa2敲除小鼠比对照小鼠病情更严重，表现为肺部细胞浸润增加，其特征是嗜酸性粒细胞和嗜碱性粒细胞的募集、黏液产生增加以及Th2细胞因子和血清IgE产生增加。因此，这些实验表明，T细胞中Foxa2的表达对于防止过敏性气道炎症中的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很重要。
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 Foxa2 from T-cells led to increased Th2 cytokine secretion and differentiation, but decreased Th1 differentiation and IFN-γ expression in vitro. 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.
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DOI：
10.4168/aair.2016.8.2.170
发表时间：
2016-03
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Jiang N;Yin J;Wen L
通讯作者：
Wen L
先驱转录因子 Foxa1 和 Foxa2 在胸腺细胞正选择过程中调节选择性 RNA 剪接。
DOI：
10.1242/dev.199754
发表时间：
2021-08-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Lau CI;Rowell J;Yanez DC;Solanki A;Ross S;Ono M;Crompton T
通讯作者：
Crompton T
DOI：
10.12703/r/10-30
发表时间：
2021
期刊：
Faculty reviews
影响因子：
--
作者：
Butcher MJ;Zhu J
通讯作者：
Zhu J
影响因子：
56.9
作者：
Hwang, ES;Szabo, SJ;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
20.3
作者：
Hager-Theodorides, AL;Dessens, JT;Crompton, T
通讯作者：
Crompton, T