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The initiation and progression of allergic asthma (AA) are associated with complex interactions between inflammation and immune response. Herein, we report the specific mechanisms underlying the molecular action of interferon (IFN)- γ in AA regulation. We speculated that IFN- γ inhibits Th9 differentiation by regulating the secretion of interleukin (IL)-27 from dendritic cells (DCs), thereby suppressing airway inflammation in asthma. We constructed a mouse model of ovalbumin-induced AA and overexpressed IFN- γ to evaluate the effect on the IL-27/Th9 axis via the in vitro effect of IFN- γ on IL-27 secretion by DCs and their influence on Th9 differentiation and asthmatic inflammation. IFN- γ overexpression reduced the proportion of Th9 cells and DCs and altered lung morphology and cytokine production in AA-induced mice, thus suppressing the AA phenotype. In addition, exogenous IFN- γ stimulation promoted the secretion of IL-27 and suppressed Th9 differentiation of CD4+ T cells via signal transducer and activator of transcription 1/3 (STAT1/3) signaling in a time-dependent manner. This study aimed to clarify the regulatory effect and mechanism of the IFN- γ /DCs/IL-27/Th9 axis on AA and provide novel insights for effective targeted treatment of asthma., Competing Interests: The authors declared that they have no conflict of interest., (Copyright © 2022 Peng Xiong et al.)

Objective: To investigate the effect of IL-27 on Th9 differentiation and Th1/Th2 balance., Methods: C57BL/6 (B6) mice were treated with ovalbumin to establish an allergic asthma (AA) model and subjected to IL-27 overexpression (OV) and empty vector (EV). Hematoxylin-eosin (HE) staining was performed to observe lung tissue inflammation. Flow cytometry was carried out to evaluate the percentage of Th9, Th1, and Th2 cells. The expression of IL-27, IL-27R, IL-9, T-bet, IFN-γ, and IgE was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot was conducted to observe the expression of pSTAT-1 and pSTAT-3., Results: Compared with the Model group, the number of Th1 cells in the Model + OV group increased significantly ( p  < .05), while those of Th9 and Th2 cells decreased significantly ( p  < .05). The expression of IL-27, IL-27R, and IFN-γ in blood serum was increased ( p  < .05), and that of IL-9 and IgE was significantly decreased in the Model + OV group compared to the Model ( p  < .05). Western blot revealed that Model + OV exhibited lower expression of pSTAT-3 than that in the Model and Model + EV groups ( p  < .05), while pSTAT-1 expression was significantly increased ( p  < .05). Inflammatory infiltration in the Model + OV group was significantly reduced, and there was no significant difference between the Model and Model + EV groups., Conclusions: IL-27 OV inhibits Th9 differentiation and regulates the imbalance of Th1/Th2, thereby alleviating inflammatory response in AA. The findings suggest that IL-27 OV may be a potential strategy for clinical treatment of AA.