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低聚果糖可改变变应性患者的树突状细胞成熟和花生诱导的自身 T 细胞反应。

Fructo-Oligosaccharides Modify Human DC Maturation and Peanut-Induced Autologous T-Cell Response of Allergic Patients .

机构信息

Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.

出版信息

Front Immunol. 2021 Feb 15;11:600125. doi: 10.3389/fimmu.2020.600125. eCollection 2020.

Abstract

BACKGROUND

Dendritic cells (DCs) play an important role in antigen presentation, and are an interesting target for immune-modulation in allergies. Short- and long-chain fructo-oligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation.

OBJECTIVE

This study investigated the effect of FF during DC maturation and allergen presentation using cells of peanut-allergic patients in an autologous DC-T cell assay.

METHODS

CD14 and CD4 T cells were isolated from peanut-allergic patients. CD14 monocytes were differentiated into immature DCs (imDCs), and matured (matDCs) in the presence or absence of crude peanut-extract (CPE) and/or FF, and co-cultured in an autologous DC-T cell assay. T cell polarization, proliferation and cytokine production were measured.

RESULTS

Expression of maturation surface molecule markers on matDCs was not affected by CPE and/or FF. By contrast, the IL-10 secretion by matDCs increased compared to imDCs, upon exposure to CPE and FF compared to CPE alone. Also the IP-10 secretion increased in CPE/FF-matDCs compared to imDC. CPE-matDCs enhanced IL-13 release in the DC-T-cell assay and Treg polarization in presence or absence of FF. CPE/FF-DCs tended to increase the Treg/Th1 and Treg/Th2 ratios compared to matDCs. The proliferation of both Treg and Th2 cells tended to increase when T cells were co-cultured with CPE-matDCs compared to matDCs, which became significant when CPE-matDCs were also exposed to FF and a same tendency was shown for Th1 proliferation.

CONCLUSION

Only in the presence of FF, CPE-matDCs produced increased regulatory and Th1-related mediators. CPE-matDCs modified T cell polarization and proliferation, and additional exposure to FF tended to enhance Treg/Th2 and Treg/Th1 ratios instructed by CPE/FF-matDCs. However this effect was not strong enough to suppress CPE-matDCs induced IL-13 release by Th-cells. This indicates the ability of FF to modify DC maturation in the presence of an allergen supporting a more Treg/Th1 prone direction of the successive allergen specific Th2 cell response.

摘要

背景

树突状细胞(DCs)在抗原呈递中发挥重要作用,是过敏免疫调节的一个有趣靶点。短链和长链果寡糖(scFOS/lcFOS,FF)具有免疫调节能力,可能影响 DC 抗原呈递的结果。

目的

本研究通过花生过敏患者的自体 DC-T 细胞检测,研究 FF 在 DC 成熟和变应原呈递过程中的作用。

方法

从花生过敏患者中分离 CD14 和 CD4 T 细胞。CD14 单核细胞分化为未成熟 DC(imDCs),并在存在或不存在粗花生提取物(CPE)和/或 FF 的情况下成熟(matDCs),并在自体 DC-T 细胞检测中进行共培养。测量 T 细胞极化、增殖和细胞因子产生。

结果

CPE 和/或 FF 对 matDCs 表面成熟分子标志物的表达没有影响。相比之下,与仅 CPE 相比,暴露于 CPE 和 FF 时 matDCs 分泌的 IL-10 增加。与 imDC 相比,CPE/FF-matDCs 中 IP-10 的分泌也增加。CPE-matDCs 在存在或不存在 FF 的情况下,在 DC-T 细胞检测中增强 IL-13 的释放并促进 Treg 极化。与 matDCs 相比,CPE/FF-DC 倾向于增加 Treg/Th1 和 Treg/Th2 比值。与 matDCs 相比,当 T 细胞与 CPE-matDCs 共培养时,Treg 和 Th2 细胞的增殖均有增加的趋势,当 CPE-matDCs 也暴露于 FF 时,这种趋势变得显著,Th1 增殖也呈现出相同的趋势。

结论

只有在 FF 的存在下,CPE-matDCs 才会产生增加的调节性和 Th1 相关介质。CPE-matDCs 改变了 T 细胞的极化和增殖,并且额外暴露于 FF 倾向于增强由 CPE/FF-matDCs 指导的 Treg/Th2 和 Treg/Th1 比值。然而,这种影响还不足以抑制 CPE-matDCs 诱导 Th 细胞产生的 IL-13。这表明 FF 具有在过敏原存在的情况下调节 DC 成熟的能力,支持随后的变应原特异性 Th2 细胞反应向更倾向于 Treg/Th1 的方向发展。

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