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L-阿拉伯糖通过调节小鼠Th1/Th2平衡和上调调节性T细胞减轻麦醇溶蛋白诱导的食物过敏。

l-Arabinose Attenuates Gliadin-Induced Food Allergy via Regulation of Th1/Th2 Balance and Upregulation of Regulatory T Cells in Mice.

作者信息

Wang Yu, Sun Juan, Xue Lamei, Liu Jinxin, Nie Chenzhipeng, Fan Mingcong, Qian Haifeng, Zhang Duo, Ying Hao, Li Yan, Wang Li

机构信息

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia 30912, United States.

出版信息

J Agric Food Chem. 2021 Mar 31;69(12):3638-3646. doi: 10.1021/acs.jafc.0c07167. Epub 2021 Mar 18.

DOI:10.1021/acs.jafc.0c07167
PMID:33734700
Abstract

Gliadins are the main cause of wheat allergies, and the prevalence of gliadin allergy has increased in many countries. l-Arabinose, a kind of plant-specific five-carbon aldose, possesses beneficial effects on food allergy to gliadins. This study investigated the antiallergic activities and underlying mechanisms of l-arabinose in a wheat gliadin-sensitized mouse model. BALB/c mice were sensitized to gliadin by intraperitoneal injections with gliadin followed by being given a gliadin challenge. l-arabinose-treated mice exhibited a marked reduction in the productions of total immunoglobulin E (IgE), gliadin-specific IgE, gliadin-specific IgG1, and histamine, with an increase in IgG2a level as compared with gliadin-sensitized mice. Beside that, a significant decrease in Th2-related cytokine level, IL-4, and an increase in Th1-related cytokine level, IFN-γ, in the serum and splenocytes were observed after treatment with l-arabinose. l-Arabinose treatment also improved the imbalance of Th1/Th2 immune response on the basis of the expression levels of related cytokines and key transcription factors in the small intestine and spleen of sensitized mice. In addition, gliadin-induced intestinal barrier impairment was blocked by l-arabinose treatment via regulation of TJ proteins and suppression of p38 MAPK and p65 NF-κB inflammation signaling pathways. Notably, the results confirmed that l-arabinose treatment increased CD4 Foxp3 T cell populations and Treg-related factors associated with increased expression of IL-2 and activation of STAT5 in gliadin-sensitized mice. In conclusion, l-arabinose attenuated the gliadin-induced allergic symptoms via maintenance of Th1/Th2 immune balance and regulation of Treg cells in a gliadin-induced mouse model, suggesting l-arabinose could be used as a promising agent to alleviate gliadin allergy.

摘要

麦醇溶蛋白是小麦过敏的主要原因,在许多国家,麦醇溶蛋白过敏的患病率呈上升趋势。L-阿拉伯糖是一种植物特有的五碳醛糖,对麦醇溶蛋白食物过敏具有有益作用。本研究在小麦醇溶蛋白致敏小鼠模型中研究了L-阿拉伯糖的抗过敏活性及其潜在机制。通过腹腔注射麦醇溶蛋白使BALB/c小鼠致敏,随后给予麦醇溶蛋白激发。与麦醇溶蛋白致敏小鼠相比,L-阿拉伯糖处理的小鼠总免疫球蛋白E(IgE)、麦醇溶蛋白特异性IgE、麦醇溶蛋白特异性IgG1和组胺的产生显著减少,IgG2a水平升高。除此之外,用L-阿拉伯糖处理后,血清和脾细胞中Th2相关细胞因子水平(IL-4)显著降低,Th1相关细胞因子水平(IFN-γ)升高。基于致敏小鼠小肠和脾脏中相关细胞因子和关键转录因子的表达水平,L-阿拉伯糖处理还改善了Th1/Th2免疫反应的失衡。此外,L-阿拉伯糖处理通过调节紧密连接蛋白以及抑制p38丝裂原活化蛋白激酶和p65核因子κB炎症信号通路,阻断了麦醇溶蛋白诱导的肠道屏障损伤。值得注意的是,结果证实L-阿拉伯糖处理增加了麦醇溶蛋白致敏小鼠中CD4 Foxp3 T细胞群体以及与IL-2表达增加和STAT5激活相关联的调节性T细胞相关因子。总之,在麦醇溶蛋白诱导的小鼠模型中,L-阿拉伯糖通过维持Th1/Th2免疫平衡和调节调节性T细胞减轻了麦醇溶蛋白诱导的过敏症状,表明L-阿拉伯糖可作为一种有前景的药物来缓解麦醇溶蛋白过敏。

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