Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma.
Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma.
复制标题
在卵清蛋白诱导的哮喘小鼠模型中，Foxp2 抑制 Th9 细胞分化并减轻过敏性气道炎症。
DOI：
10.1016/j.intimp.2022.109060
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Zhengrong Chen
中科院分区：
文献类型：
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作者：
Xinxing Zhang;Yu Ma;Yanyu He;Wenjing Gu;Yongdong Yan;Wei Ji;Li Huang;Yuqing Wang;Chuangli Hao;Gang Li;Zhengrong Chen
本研究旨在探讨叉头盒P2基因(Foxp2)对哮喘小鼠辅助性T细胞(Th9)分化的影响。用卵白蛋白(OVA)诱导小鼠体内哮喘模型。用转化生长因子-β、IL-4和抗-干扰素-γ共同培养CD_4+T细胞，建立体外模型。采用ELISA法、流式细胞仪、qRT-PCR法和Western印迹法分别检测IL-9的分泌、Th9细胞数和Th9细胞转录因子的表达。用HE和PAS糖原染色观察肺组织病理改变和呼吸道粘液分泌情况。抗IL-9单抗可逆转哮喘小鼠Th9细胞及肺组织和支气管肺泡灌洗液中IL-9的表达。哮喘小鼠BALF、肺组织和Th9细胞中Foxp2表达下调。Foxp2过表达在体外抑制Th9细胞分化，在体内改善气道炎症。我们的研究表明，Foxp2的过表达通过抑制Th9细胞的分化来减轻过敏性哮喘。
This study aimed to explore the effects of forkhead box P2 gene (Foxp2) on T-helper 9 (Th9) differentiation in asthmatic mice. An in vivo asthmatic mouse model was induced with ovalbumin (OVA). An in vitro model was established by culturing CD4+ T cells with TGF-β, IL-4, and anti-IFN-γ. ELISA, flow cytometry, qRT-PCR and Western blot were performed to examine IL-9 secretion, Th9 cell number, and Th9 cell transcription factor expression, respectively. Pathological changes in lung tissues and airway mucus secretion were assessed with HE and PAS glycogen staining. Anti-IL-9 mAb reversed the elevation in Th9 cells and IL-9 expression in lung tissues and bronchoalveolar lavage fluid (BALF) of asthmatic mice. Foxp2 was downregulated in BALF and lung tissue of asthmatic mice and Th9 cells. Overexpression of Foxp2 inhibited Th9 cell differentiation in vitro and improved airway inflammation in vivo. Our study suggests that overexpression of Foxp2 attenuates allergic asthma by inhibiting Th9 cell differentiation.