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长非编码 RNA JPX 通过靶向 miR-378g/CCL5 轴促进变应性鼻炎中 Treg/Th17 失衡。

LncRNA JPX contributes to Treg/Th17 imbalance in allergic rhinitis targeting the miR-378g/CCL5 axis.

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Immunopharmacol Immunotoxicol. 2022 Aug;44(4):519-524. doi: 10.1080/08923973.2022.2055566. Epub 2022 Apr 6.

Abstract

T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored. CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-β, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot. The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects. In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.

摘要

调节性 T 细胞(Treg)/辅助性 T 细胞 17(Th17)失衡与过敏性鼻炎(AR)的发病机制有关。长链非编码 RNA(lncRNA)参与 AR 的进展。在此,研究了 lncRNA JP X 对 AR 中 Treg/Th17 平衡的影响。从 AR 患者和健康对照中分离 CD4+T 细胞。通过流式细胞术检查 Treg 和 Th17 细胞的百分比。使用 qRT-PCR 检测 JP X、miR-378g、CCL5、TGF-β 和 IL-17A 的水平。通过 Western blot 测量 Foxp3 和 RORγt 的蛋白表达。数据表明 Treg/Th17 的失衡与 AR 有关。在 AR 中发现 JP X 上调,下调 JP X 可改善 Treg/Th17 的失衡。此外,JP X 作为 miR-378g 的海绵上调 CCL5。抑制 miR-378g 逆转了沉默 JP X 对 Treg/Th17 诱导的作用。此外,CCL5 的过表达逆转了 miR-378g 诱导的作用。总之,耗尽 JP X 通过调节 miR-378g/CCL5 轴促进 AR 中的 Treg/Th17 平衡。这些发现为 AR 提供了新的治疗思路。

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