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长链非编码 RNA FOXD3-AS1 通过调节树突状细胞升高 Th1/Th2 比值缓解变应性鼻炎

Long Non Coding RNA FOXD3‑AS1 Alleviates Allergic Rhinitis by Elevating the Th1/Th2 Ratio via the Regulation of Dendritic Cells.

机构信息

Department of Otolaryngology Head and Neck surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Immunol Invest. 2023 Nov;52(4):499-512. doi: 10.1080/08820139.2023.2197940. Epub 2023 May 2.

Abstract

This article aimed to explore whether the regulation of Th1/Th2 immune responses by FOXD3-AS1 is associated with dendritic cells (DCs) in allergic rhinitis (AR). HE staining was performed to assess the pathological changes in the nasal mucosa; ELISA was performed to measure the levels of Th1/Th2-related cytokines; flow cytometry was performed to analyze Th1/Th2 cells and MHC-II-, CD80-, and CD86-positive DCs; and qRT‒PCR and western blotting were performed to measure mRNA and protein expression levels, respectively. Our data revealed that LV-FOXD3-AS1 improved AR and increased the Th1/Th2 cell ratio in AR model mice. LV-FOXD3-AS1 further inhibited DC maturation both in vivo and in vitro. Moreover, the coculture system of DCs and CD4+ T cells demonstrated that LV-FOXD3-AS1 increased the Th1/Th2 cell ratio by inhibiting the maturation of DCs. In addition, LV-FOXD3-AS1 reduced the level of phosphorylated STAT6 in DCs derived from healthy mice, and STAT6 overexpression eliminated the inhibitory effect of LV-FOXD3-AS1 on the maturation of DCs. In summary, LV-FOXD3-AS1 ameliorated AR by increasing the Th1/Th2 cell ratio by inhibiting DC maturation via the inhibition of STAT6 phosphorylation. Our data confirmed the protective effect of FOXD3-AS1 in AR and provided a novel idea for the treatment of this disease.

摘要

本文旨在探讨 FOXD3-AS1 对 Th1/Th2 免疫反应的调节是否与变应性鼻炎 (AR) 中的树突状细胞 (DC) 有关。进行 HE 染色以评估鼻黏膜的病理变化;通过 ELISA 测量 Th1/Th2 相关细胞因子的水平;通过流式细胞术分析 Th1/Th2 细胞和 MHC-II、CD80 和 CD86 阳性 DC;通过 qRT‒PCR 和 Western blot 分别测量 mRNA 和蛋白表达水平。我们的数据显示,LV-FOXD3-AS1 改善了 AR 并增加了 AR 模型小鼠中的 Th1/Th2 细胞比例。LV-FOXD3-AS1 进一步抑制了体内和体外 DC 的成熟。此外,DC 和 CD4+T 细胞的共培养系统表明,LV-FOXD3-AS1 通过抑制 DC 的成熟增加了 Th1/Th2 细胞比例。此外,LV-FOXD3-AS1 降低了来自健康小鼠的 DC 中磷酸化 STAT6 的水平,并且 STAT6 的过表达消除了 LV-FOXD3-AS1 对 DC 成熟的抑制作用。总之,LV-FOXD3-AS1 通过抑制 STAT6 磷酸化抑制 DC 成熟来增加 Th1/Th2 细胞比例,从而改善 AR。我们的数据证实了 FOXD3-AS1 在 AR 中的保护作用,并为该疾病的治疗提供了新的思路。

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