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微小 RNA-181a 和微小 RNA-155 参与调节过敏性鼻炎患儿调节性 T 细胞的分化和功能。

MicroRNA-181a and microRNA-155 are involved in the regulation of the differentiation and function of regulatory T cells in allergic rhinitis children.

机构信息

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

Department of Respiratory Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical College, Guangzhou, China.

出版信息

Pediatr Allergy Immunol. 2019 Jun;30(4):434-442. doi: 10.1111/pai.13038. Epub 2019 Feb 27.

DOI:10.1111/pai.13038
PMID:30734973
Abstract

BACKGROUND

Regulatory T cells (Tregs) play central roles in limiting airway allergic inflammation and preventing inappropriate Th2 responses to environmental allergens. This study aims to evaluate the role of miR-181a and miR-155 in the regulation of the differentiation and function of Tregs through both in vivo and in vitro studies.

METHODS

The CD4 T cells and Tregs were purified from peripheral blood mononuclear cells (PBMCs) in allergic rhinitis (AR) children, respectively. The miR-155/181a mimics and inhibitors were transfected into CD4 T cells and Tregs. The differentiation and function of Tregs were evaluated by flow cytometry and enzyme-linked immunosorbent assay. AR mice models were established, and miR-155/181a mimics or inhibitors were injected through tail vein. The Treg percentage and function from mice were compared among different groups.

RESULTS

The miR-181a up-regulated the release of interleukin (IL)-10 and TGF-β, whereas the miR-155 promoted Treg differentiation in CD4 T cells. Similarly, we also found that miR-155 promoted Treg proliferation directly through suppressor of cytokine signaling 1 (SOCS1) and sirtuin1 (SIRT1) signaling pathway, whereas miR-181a up-regulated mRNA expression of IL-10 and TGF-β through phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. We also found that miR-155/181a affect Treg percentage and function in mice model.

CONCLUSION

Our findings suggest that miR-181a and miR-155 were closely correlated with the proliferation and function of Tregs in AR, providing new potential treatment target.

摘要

背景

调节性 T 细胞(Tregs)在限制气道变应性炎症和防止对环境变应原产生不适当的 Th2 反应方面发挥着核心作用。本研究旨在通过体内和体外研究评估 miR-181a 和 miR-155 在调节 Treg 的分化和功能中的作用。

方法

分别从过敏性鼻炎(AR)儿童的外周血单核细胞(PBMCs)中纯化 CD4 T 细胞和 Tregs。将 miR-155/181a 模拟物和抑制剂转染到 CD4 T 细胞和 Tregs 中。通过流式细胞术和酶联免疫吸附试验评估 Treg 的分化和功能。建立 AR 小鼠模型,并通过尾静脉注射 miR-155/181a 模拟物或抑制剂。比较不同组小鼠的 Treg 百分比和功能。

结果

miR-181a 上调了白细胞介素(IL)-10 和转化生长因子(TGF)-β的释放,而 miR-155 促进了 CD4 T 细胞中的 Treg 分化。同样,我们还发现 miR-155 通过细胞因子信号转导抑制因子 1(SOCS1)和沉默调节蛋白 1(SIRT1)信号通路直接促进 Treg 增殖,而 miR-181a 通过磷脂酰肌醇 3-OH 激酶(PI3K)/Akt 通路上调 IL-10 和 TGF-β的 mRNA 表达。我们还发现 miR-155/181a 影响小鼠模型中 Treg 的百分比和功能。

结论

我们的研究结果表明,miR-181a 和 miR-155 与 AR 中 Treg 的增殖和功能密切相关,为新的潜在治疗靶点提供了依据。

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