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利用Caco-2/免疫细胞共培养模型研究大豆过敏原Gly m 4的致敏潜力

Investigation of Sensitization Potential of the Soybean Allergen Gly m 4 by Using Caco-2/Immune Cells Co-Culture Model.

作者信息

Bogdanov Ivan V, Finkina Ekaterina I, Melnikova Daria N, Ziganshin Rustam H, Ovchinnikova Tatiana V

机构信息

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997 Moscow, Russia.

出版信息

Nutrients. 2021 Jun 16;13(6):2058. doi: 10.3390/nu13062058.

Abstract

The soybean allergen Gly m 4 is known to cause severe allergic reactions including anaphylaxis, unlike other Bet v 1 homologues, which induce mainly local allergic reactions. In the present study, we aimed to investigate whether the food Bet v 1 homologue Gly m 4 can be a sensitizer of the immune system. Susceptibility to gastrointestinal digestion was assessed . Transport through intestinal epithelium was estimated using the Caco-2 monolayer. Cytokine response of different immunocompetent cells was evaluated by using Caco-2/Immune cells co-culture model. Absolute levels of 48 cytokines were measured by multiplex xMAP technology. It was shown that Gly m 4 can cross the epithelial barrier with a moderate rate and then induce production of IL-4 by mature dendritic cells . Although Gly m 4 was shown to be susceptible to gastrointestinal enzymes, some of its proteolytic fragments can selectively cross the epithelial barrier and induce production of Th2-polarizing IL-5, IL-10, and IL-13, which may point at the presence of the T-cell epitope among the crossed fragments. Our current data indicate that Gly m 4 can potentially be a sensitizer of the immune system, and intercommunication between immunocompetent and epithelial cells may play a key role in the sensitization process.

摘要

大豆过敏原Gly m 4已知会引发包括过敏反应在内的严重过敏反应,这与其他主要引发局部过敏反应的Bet v 1同源物不同。在本研究中,我们旨在调查食物中的Bet v 1同源物Gly m 4是否会成为免疫系统的致敏原。评估了其对胃肠道消化的敏感性。使用Caco-2单层细胞评估其通过肠上皮的转运情况。通过Caco-2/免疫细胞共培养模型评估不同免疫活性细胞的细胞因子反应。采用多重xMAP技术测量48种细胞因子的绝对水平。结果表明,Gly m 4能够以中等速率穿过上皮屏障,然后诱导成熟树突状细胞产生IL-4。尽管Gly m 4对胃肠道酶敏感,但其一些蛋白水解片段能够选择性地穿过上皮屏障,并诱导产生Th2极化的IL-5、IL-10和IL-13,这可能表明在穿过的片段中存在T细胞表位。我们目前的数据表明,Gly m 4可能是免疫系统的致敏原,免疫活性细胞与上皮细胞之间的相互作用可能在致敏过程中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b1/8234232/89cda2f953d2/nutrients-13-02058-g001.jpg

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