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.

变应性鼻炎（AR）是一种常见的变态反应性疾病，其特征是促进CD4 ⁺ T细胞的Th2分化。然而，Th2分化的潜在机制仍不清楚。非编码RNA在Th2分化中起关键作用，而很少有研究揭示长非编码RNA，环状RNA和microRNA之间的相互作用。在这项研究中，与健康对照组相比，比较了AR患者和实验诱发的AR小鼠鼻黏膜样品中几种circRNA和lncRNA的差异表达。结果表明，高表达的CircHIPK3和LncGAS5促进卵清蛋白诱导的CD4 ^+的Th2分化。AR小鼠的T细胞和鼻部症状加重。我们还发现CircHIPK3和LncGAS5通过调节它们共同的靶标miR-495诱导Th2细胞特异性转录因子GATA-3的上调。同时，鼻内施用CircHIPK3或LncGAS5敲低慢病毒可减轻AR小鼠的鼻部症状。总之，我们的发现表明，CircHIPK3，LncGAS5和miR-495之间的相互作用在AR中Th2分化的调控中起着关键作用。