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

Immunosuppressive Regulation of Dendritic Cells and T Cells in Allergic Rhinitis by Semaphorin 3A
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Semaphorin 3A 对过敏性鼻炎中树突状细胞和 T 细胞的免疫抑制调节

DOI:
10.1177/19458924211005592
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发表时间:
2021-03
影响因子:
2.6
通讯作者:
Tan Guolin
Tan Guolin
中科院分区:
医学3区
文献类型:
--
作者:
Liu Honghui;Xia Jinye;Chen Yu;Ai Jingang;Wang Tiansheng;Tan Guolin

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研究背景Semaphrin 3A(Sema 3A)在自身免疫性疾病中起重要的免疫调节作用,在变态反应性疾病中也有重要意义。然而,Sema 3A对变应性鼻炎(AR)的作用尚不完全清楚。目的探讨Sema 3A对变应性鼻炎(AR)中树突状细胞(DC)和幼稚CD 4 + T细胞的调节作用。方法采用免疫组织化学染色和蛋白质印迹法检测Sema 3A在正常鼻黏膜中的表达。采用Ficoll-Hypaque法分离人外周血单个核细胞。通过磁性选择纯化DC和初始CD 4 + T细胞。在体外将人Sema 3A Fc嵌合体添加到DC和初始CD 4 + T细胞中以评估Sema 3A对DC和T细胞功能的影响。用CFSE标记T细胞用于测定细胞增殖。流式细胞术检测DC成熟标志物(CD 40和CD 83)、辅助性T细胞17(Th 17)和调节性T细胞(Treg)的百分比。ELISA法检测IL 10、IL 17、IL 4和IFNγ细胞因子水平。结果Sema 3A在变应性鼻炎下鼻甲组织中的表达低于正常对照组织。与健康对照DC相比,AR DC在Sema 3A处理后显示DC成熟标志物CD 40和CD 83的水平降低。此外,Sema 3A降低了AR中的初始CD 4 + T细胞增殖。此外,Sema 3A还能增加Th 17细胞的百分率,但对Th 17细胞的百分率无明显影响。Sema 3A可显著提高IL 10和IFNγ水平,降低IL 4水平,但对IL 17水平无明显影响。结论AR患者鼻黏膜组织中Sema 3A低表达,Sema 3A可抑制DC成熟、T细胞增殖和Treg极化。
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.
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发表时间: 2015
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发表时间: 2003-05-01
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影响因子: 14.2
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DOI: 10.1016/j.clim.2017.05.011
发表时间: 2017-11
影响因子: 8.6
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