DNMT3A-mediated Methylation of IRF4 Alleviates Inflammatory Response in Allergic Rhinitis Mice.

Abstract

This study explores the mechanism of DNMT3A in inflammatory response in allergic rhinitis (AR) mice. A mouse model of AR was established by ovalbumin induction, followed by injection of DNMT3A overexpression vector. The times of nose rubbing and sneezing within 15 min were recorded. The nasal mucosa tissues were observed by H&E staining. The serum histamine, IgE, IL-1β, IL-10, IFN-γ, and TNF-α were detected by ELISA. The proportion of Th17/Treg cells in lymphocytes was detected by flow cytometry. DNMT3A, IRF4, and CD44 expressions were tested by qRT-PCR or Western blot. ChIP evaluated the DNMT3A enrichment on IRF4 promoter and IRF4 enrichment on CD44 promoter. Methylation-specific PCR determined the methylation level of IRF4 promoter. The binding of IRF4 to CD44 was verified by dual-luciferase assay. DNMT3A was poorly expressed in AR mice. DNMT3A overexpression reduced the times of nose rubbing and sneezing in AR mice, alleviated nasal mucosal tissue injury, reduced the proportion of Th17/Treg cells, and diminished serum inflammatory factors. DNMT3A was enriched on IRF4 promoter and repressed IRF4 expression by enhancing IRF4 methylation level. IRF4 bound to CD44 promoter to elevate CD44 expression. In conclusion, DNMT3A-mediated methylation of IRF4 reduces AR inflammatory response by elevating CD44 expression.