Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Cell Death Dis. 2020 Apr 2;11(4):216. doi: 10.1038/s41419-020-2394-3.
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）是一种常见的过敏性疾病，其特征在于促进 CD4 T 细胞向 Th2 分化。然而，Th2 分化的机制尚不清楚。非编码 RNA 在 Th2 分化中发挥着关键作用，然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，比较了 AR 患者和实验性诱导 AR 的小鼠鼻黏膜样本中几种 circRNAs 和 lncRNAs 的差异表达情况，与健康对照组相比。结果表明，高表达的 CircHIPK3 和 LncGAS5 促进了卵清蛋白诱导的 CD4 T 细胞的 Th2 分化，并加重了 AR 小鼠的鼻症状。我们还发现 CircHIPK3 和 LncGAS5 通过调节其共同的靶标 miR-495 诱导 Th2 细胞特异性转录因子 GATA-3 的上调。同时，CircHIPK3 或 LncGAS5 敲低慢病毒的鼻腔内给药减少了 AR 小鼠的鼻症状。总之，我们的研究结果表明，CircHIPK3、LncGAS5 和 miR-495 之间的相互作用在 AR 中 Th2 分化的调节中起着关键作用。
