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信号素 3A 对变应性鼻炎树突状细胞和 T 细胞的免疫抑制调节作用。

Immunosuppressive Regulation of Dendritic Cells and T Cells in Allergic Rhinitis by Semaphorin 3A.

机构信息

Department of Otorhinolaryngology - Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, P.R. China.

出版信息

Am J Rhinol Allergy. 2021 Nov;35(6):846-853. doi: 10.1177/19458924211005592. Epub 2021 Mar 24.

DOI:10.1177/19458924211005592
PMID:33761786
Abstract

BACKGROUND

Semaphrin3A (Sema3A) was found to play a major role in immune regulation in autoimmune diseases and to be of importance in allergic disease. However, the effect of Sema3A on allergic rhinitis (AR) is not fully clear.

OBJECTIVE

We sought to elucidate the effects of Sema3A on the regulation of dendritic cells (DCs) and naive CD4 T cells in AR.

METHODS

The expression of Sema3A in nasal mucosa was measured by immunohistochemical staining and western blotting. Human peripheral blood mononuclear cells were separated by the Ficoll-Hypaque method. DCs and naive CD4 T cells were purified by magnetic selection. A human Sema3A Fc chimera was added to DCs and naive CD4 T cells in vitro to evaluate the effect of Sema3A on the function of DCs and T cells. Labeling T cells with CFSE was used to determine cell proliferation. Flow cytometry was used to detect the DC maturation markers (CD40 and CD83) and T helper 17 (Th17) and regulatory T cell (Treg) percentages. ELISA was used to detect the IL10, IL17, IL4, and IFNγ cytokine levels.

RESULTS

The expression of Sema3A in AR inferior turbinate tissue was lower than that in healthy control tissue. Compared with healthy control DCs, AR DCs showed decreased levels of the DC maturation markers CD40 and CD83 after Sema3A treatment. Furthermore, Sema3A decreased naive CD4 T cell proliferation in AR. In addition, Sema3A increased the percentage of Tregs but had no obvious effect on Th17 cells. Moreover, Sema3A significantly increased levels of IL10 and IFNγ, and decreased level of IL4, but had no obvious effect on level of IL17.

CONCLUSION

AR presented with low expression of Sema3A in nasal mucosa, and Sema3A could decrease DC maturation, T cell proliferation, and Treg polarization.

摘要

背景

Semaphrin3A(Sema3A)在自身免疫性疾病的免疫调节中发挥重要作用,在过敏性疾病中也具有重要意义。然而,Sema3A 对过敏性鼻炎(AR)的影响尚不完全清楚。

目的

我们旨在阐明 Sema3A 对 AR 中树突状细胞(DC)和幼稚 CD4 T 细胞调节的影响。

方法

通过免疫组织化学染色和 Western blot 检测鼻黏膜中 Sema3A 的表达。采用 Ficoll-Hypaque 法分离人外周血单个核细胞,采用磁珠分选法纯化 DC 和幼稚 CD4 T 细胞。体外将人 Sema3A Fc 嵌合体加入 DC 和幼稚 CD4 T 细胞中,评估 Sema3A 对 DC 和 T 细胞功能的影响。用 CFSE 标记 T 细胞以确定细胞增殖。流式细胞术检测 DC 成熟标志物(CD40 和 CD83)和 T 辅助 17(Th17)和调节性 T 细胞(Treg)的百分比。ELISA 法检测 IL10、IL17、IL4 和 IFNγ 细胞因子水平。

结果

AR 下鼻甲组织中 Sema3A 的表达低于健康对照组织。与健康对照 DC 相比,AR DC 在 Sema3A 处理后其 DC 成熟标志物 CD40 和 CD83 的水平降低。此外,Sema3A 降低了 AR 幼稚 CD4 T 细胞的增殖。此外,Sema3A 增加了 Treg 的百分比,但对 Th17 细胞没有明显影响。此外,Sema3A 显著增加了 IL10 和 IFNγ 的水平,降低了 IL4 的水平,但对 IL17 的水平没有明显影响。

结论

AR 鼻黏膜中 Sema3A 表达降低,Sema3A 可降低 DC 成熟、T 细胞增殖和 Treg 极化。

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