RBM15 exacerbates airway inflammation in asthma by activating NF-κB through the m6A-YTHDF2 axis

m 6 A methylation modification participates in the regulation of inflammatory responses, whereas the specific role and related mechanism of its cofactor RBM15 in asthma remain poorly defined. This study aimed to explore the function of RBM15 in allergic asthma and further elucidate its molecular mechanism regulating the NF-κB pathway through the m 6 A-YTHDF2-TNFAIP3 axis. In this research, an OVA-induced mouse allergic asthma model was established to detect RBM15 expression and assess the influences of RBM15 knockdown on airway inflammation, airway hyperresponsiveness and Th2 immune response. Besides, TNF-α was applied to construct an in vitro inflammatory model of airway epithelial cells. Western blot, mRNA stability detection, m 6 A-MeRIP-qPCR and RIP-qPCR were adopted to explore the mechanism by which RBM15 modulates TNFAIP3, and YTHDF2 complementation experiment was performed to confirm the function of this regulatory axis. The results revealed that RBM15 was highly expressed in lung tissues of asthmatic mice. Silencing RBM15 could alleviate airway inflammation, decrease serum IgE and Th2 cytokine levels, and ameliorate airway hyperresponsiveness. In vitro assays verified that RBM15 elevated the m 6 A modification level of TNFAIP3 mRNA, thereby facilitating YTHDF2-dependent degradation of TNFAIP3 mRNA, suppressing TNFAIP3 expression and triggering NF-κB pathway activation. RBM15 knockdown recovered TNFAIP3 expression and blocked NF-κB signaling, and such changes could be rescued by YTHDF2 overexpression. Collectively, inhibition of RBM15 relieves airway inflammation and airway hyperresponsiveness in allergic asthma via the m 6 A-YTHDF2-TNFAIP3 axis.