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微小RNA-375通过胸腺基质淋巴细胞生成素对变应性鼻炎中2型固有淋巴细胞的调控

MicroRNA-375-mediated regulation of ILC2 cells through TSLP in allergic rhinitis.

作者信息

Luo Xi, Zeng Qingxiang, Yan Shengbao, Liu Wenlong, Luo Renzhong

机构信息

Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

出版信息

World Allergy Organ J. 2020 Aug 9;13(8):100451. doi: 10.1016/j.waojou.2020.100451. eCollection 2020 Aug.

Abstract

BACKGROUND

Studies have shown that the number and function of type II innate lymphoid cells (ILC2) in peripheral blood of allergic rhinitis (AR) children increased significantly. This study aims to evaluate the role of miR-375 in the regulation of the differentiation and function of ILC2 through both and studies.

METHODS

The expression of miR-375, thymic stromal lymphopoietin (TSLP) and the frequency of ILC2 were detected and compared between AR children and controls by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbnent assay (ELISA) and flow cytometry, respectively. The miR-375 mimics or inhibitors were transfected into human nasal epithelial cells (HNECs), and the production of TSLP was detected by ELISA. HNECs and ILC2s were co-cultured to explore the role of miR-375 on ILC2s. AR mice models were established to prove the effect of miR-375 on ILC2s .

RESULTS

The expression of TSLP, miR-375, and the frequency of ILC2 were significantly higher in AR compared with controls. We found that the TSLP expression by HNECs were significantly higher when transfected with miR-375 mimics than in those transfected with miR-control and miR-375 inhibitor. In the coculture system, HNECs transfected with miR-375 mimics promote the type II cytokines production by ILC2, and this effect was blocked by anti-TSLP. Our results also showed that the miR-375 inhibitors attenuate allergic symptoms and production of type II cytokines in AR mice.

CONCLUSIONS

Our findings suggest that miR-375-mediated regulation of ILC2 cells through TSLP, providing new potential treatment target for AR.

摘要

背景

研究表明,过敏性鼻炎(AR)患儿外周血中II型天然淋巴细胞(ILC2)的数量和功能显著增加。本研究旨在通过体内和体外研究评估miR-375在调节ILC2分化和功能中的作用。

方法

分别采用实时聚合酶链反应(PCR)、酶联免疫吸附测定(ELISA)和流式细胞术检测并比较AR患儿和对照组中miR-375、胸腺基质淋巴细胞生成素(TSLP)的表达以及ILC2的频率。将miR-375模拟物或抑制剂转染到人鼻上皮细胞(HNECs)中,通过ELISA检测TSLP的产生。将HNECs与ILC2s共培养以探讨miR-375对ILC2s的作用。建立AR小鼠模型以证明miR-375对ILC2s的影响。

结果

与对照组相比,AR患者中TSLP、miR-375的表达以及ILC2的频率显著更高。我们发现,用miR-375模拟物转染的HNECs中TSLP的表达显著高于用miR-对照和miR-375抑制剂转染的细胞。在共培养系统中,用miR-375模拟物转染的HNECs促进ILC2产生II型细胞因子,而抗TSLP可阻断这种作用。我们的结果还表明,miR-375抑制剂可减轻AR小鼠的过敏症状和II型细胞因子的产生。

结论

我们的研究结果表明,miR-375通过TSLP介导对ILC2细胞的调节,为AR提供了新的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2238/7419668/780cb811c20a/gr1.jpg

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