Cyp2e1 protects against OVA-induced allergic rhinitis through the inhibition of Th2 cell activation and differentiation: Mediated by MAFB

Abstract

Allergic rhinitis (AR) is a common allergic disease. Cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) is a member of the cytochrome P450 family of enzymes, while its role in AR is still unveiled. In AR mice, T cell-specific overexpression of Cyp2e1 relieved the AR symptoms. Overexpressed-Cyp2e1 restrained the infiltration of eosinophils and mast cells in the nasal mucosa of mice, and the inflammatory cells in nasal lavage fluid (NALF). Cyp2e1 overexpressed mice exhibited decreased goblet cell hyperplasia and mucus secretion as well as decreased MUC5AC expression in nasal mucosa. The epithelial permeability and integrity of nasal mucosa were improved upon Cyp2e1 overexpression in AR mice, as evidenced by decreased fluorescein isothiocyanate-dextran 4 content in serum, increased expression of IL-25, IL-33, and TSLP in NALF, and increased expression of ZO-1 and occluding in nasal mucosa. Cyp2e1 inhibited Th2 immune response by decreasing the expression and secretion of IL-4, IL-5, and IL-13 as well as the expression of GATA-3 in NALF or nasal mucosa. We proved that Cyp2e1 inhibited the differentiation of naïve CD4⁺ T cells toward the Th2 subtype, which was regulated by MAFB by binding to Cyp2e1 promoter to activate its transcription. Overall, these results show the potential role of Cyp2e1 in alleviating AR symptoms by restraining CD4⁺ T cells to Th2 cell differentiation. Our findings provide further insight into the AR mechanism.

Keywords: Allergic rhinitis; Cyp2e1; MAFB; Th2 cell differentiation.