The imbalance of helper T cell (Th) 1/Th2 differentiation is involved in the development of allergic rhinitis (AR). Recent studies reveal the regulatory function of exosomes on Th1/Th2 differentiation. However, the key mediator in exosomes that modulate such response remains unclear. In this study, the expression of long-noncoding RNA GAS5 (LncGAS5) was detected in exosomes which were isolated from AR patient nasal mucus (AR-EXO) and ovalbumin (OVA)-stimulated nasal epithelial cells (OVA-EXO). Th1/Th2 differentiation was induced in naïve CD4+ T cells, and the percentage of IFN-γ expressing cells (Th1 cells) and IL-4 expressing cells (Th2 cells) was detected using flow cytometry. The result showed that LncGAS5 was upregulated in AR epithelial samples, AR-EXO, and OVA-EXO. The coincubation of AR-EXO and CD4+ T cells suppressed Th1 differentiation and promoted Th2 differentiation, which is mediated by LncGAS5 in AR-EXO. The LncGAS5 in AR-EXO inhibited transcription and expression of EZH2, and it also inhibited T-bet expression at mRNA and protein levels. The gain-of-function and loss-of-function experiments suggested that LncGAS5 mediates Th1/Th2 differentiation partly through downregulating T-bet and EZH2. In summary, our findings demonstrated that LncGAS5 in AR epithelium-derived exosomes is the key mediator in Th1/Th2 differentiation, providing a possible therapeutic target of AR.

中文翻译：

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外泌体长链非编码RNA GAS5通过下调过敏性鼻炎中的EZH2和T-bet来抑制Th1分化并促进Th2分化。

辅助性 T 细胞 (Th) 1/Th2 分化的失衡与过敏性鼻炎 (AR) 的发展有关。最近的研究揭示了外泌体对 Th1/Th2 分化的调节功能。然而，外泌体中调节这种反应的关键介质仍不清楚。在这项研究中，在从 AR 患者鼻粘液 (AR-EXO) 和卵清蛋白 (OVA) 刺激的鼻上皮细胞 (OVA-EXO) 中分离的外泌体中检测到长链非编码 RNA GAS5 (LncGAS5) 的表达。在幼稚 CD4+ T 细胞中诱导 Th1/Th2 分化，并使用流式细胞术检测 IFN-γ 表达细胞（Th1 细胞）和 IL-4 表达细胞（Th2 细胞）的百分比。结果表明，LncGAS5 在 AR 上皮样品、AR-EXO 和 OVA-EXO 中上调。AR-EXO 和 CD4+ T 细胞的共培养抑制了 Th1 分化并促进了 Th2 分化，这是由 AR-EXO 中的 LncGAS5 介导的。AR-EXO 中的 LncGAS5 抑制了 EZH2 的转录和表达，并且还在 mRNA 和蛋白质水平上抑制了 T-bet 的表达。功能获得和功能丧失实验表明 LncGAS5 部分通过下调 T-bet 和 EZH2 介导 Th1/Th2 分化。总之，我们的研究结果表明，AR 上皮衍生的外泌体中的 LncGAS5 是 Th1/Th2 分化的关键介质，为 AR 提供了可能的治疗靶点。功能获得和功能丧失实验表明 LncGAS5 部分通过下调 T-bet 和 EZH2 介导 Th1/Th2 分化。总之，我们的研究结果表明，AR 上皮衍生的外泌体中的 LncGAS5 是 Th1/Th2 分化的关键介质，为 AR 提供了可能的治疗靶点。功能获得和功能丧失实验表明 LncGAS5 部分通过下调 T-bet 和 EZH2 介导 Th1/Th2 分化。总之，我们的研究结果表明，AR 上皮衍生的外泌体中的 LncGAS5 是 Th1/Th2 分化的关键介质，为 AR 提供了可能的治疗靶点。