The regulatory network among CircHIPK3, LncGAS5, and miR-495 promotes Th2 differentiation in allergic rhinitis

Allergic rhinitis (AR) is a common allergic disease which is characterized by the promotion of Th2 differentiation of CD4⁺ T cells. However, the mechanisms underlying Th2 differentiation remain unclear. Non-coding RNAs play a critical role in Th2 differentiation, whereas few studies have revealed the interactions among long non-coding RNAs, circular RNAs, and microRNAs. In this study, the differential expressions of several circRNAs and lncRNAs were compared in nasal mucosa samples of AR patients and mice with experimentally induced AR as compared to healthy controls. The results showed that the highly expressed CircHIPK3 and LncGAS5 promoted Th2 differentiation of ovalbumin-induced CD4⁺ T cells and aggravated nasal symptoms of AR mice. We also found that CircHIPK3 and LncGAS5 induced the upregulation of Th2 cell-specific transcript factor GATA-3 via modulating their common target miR-495. Meanwhile, the intranasal administration of CircHIPK3 or LncGAS5 knockdown lentivirus decreased nasal symptoms of AR mice. In conclusion, our findings indicated that the interactions among CircHIPK3, LncGAS5, and miR-495 play a critical role in the regulation of Th2 differentiation in AR.