Foxp2 inhibits Th9 cell differentiation and attenuates allergic airway inflammation in a mouse model of ovalbumin-induced asthma

• DOI: 10.1016/j.intimp.2022.109060
• Publication Date: 2022-08-02T18:32:35Z
• Authors: Xinxing Zhang; Yu Ma; Yanyu He; Wenjing Gu; Yongdong Yan; Wei Ji; Li Huang; Yuqing Wang; Chuangli Hao; Gang Li; Zhengrong Chen
• Keywords: Inflammation; 0301 basic medicine; Mice, Inbred BALB C; Ovalbumin; Cell Differentiation; Forkhead Transcription Factors; T-Lymphocytes, Helper-Inducer; Asthma; 3. Good health; Repressor Proteins; Disease Models, Animal; Mice; 03 medical and health sciences; Animals; Bronchoalveolar Lavage Fluid; Lung

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.