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口服磷酸化低致敏变应原免疫治疗比完整变应原更有效地改善荞麦过敏的小鼠模型中的过敏反应。

Oral Immunotherapy with a Phosphorylated Hypoallergenic Allergen Ameliorates Allergic Responses More Effectively Than Intact Allergen in a Murine Model of Buckwheat Allergy.

机构信息

Department of Bioscience and Biotechnology, Shinshu University, Kamiina, Nagano, 399-4598, Japan.

Interdisciplinary Cluster for Cutting Edge, Shinshu University, Kamiina, Nagano, 399-4598, Japan.

出版信息

Mol Nutr Food Res. 2018 Nov;62(21):e1800303. doi: 10.1002/mnfr.201800303. Epub 2018 Sep 14.

Abstract

SCOPE

Buckwheat is a common food allergen frequently consumed in Asian countries, with Fag e 1 and Fag e 2 being the major buckwheat allergens. The purpose of this study is to prepare an oral immunotherapy agent by attenuating these allergens via phosphorylation. The immunomodulatory effects of phosphorylated Fag e 2 (P-Fag e 2) in a mouse model of buckwheat allergy are evaluated.

METHODS AND RESULTS

Phosphorylated Fag e 1 (P-Fag e 1) and P-Fag e 2 are prepared by dry-heating in the presence of pyrophosphate. Subsequent dot-blot analysis using serum from food-allergic patient indicates that both proteins exhibit reduced allergenicity upon phosphorylation. Mice subjected to oral administration of P-Fag e 2 for 6 weeks exhibit decreased specific serum IgE and increased specific IgA after Fag e 2 sensitization compared to the sham-treated mice. Moreover, the Peyer's patches (PP) of phosphorylated antigen-fed mice show decreased IL-4 production and induction of T follicular helper (Tfh) cells. Increased production of IL-6 is observed in the CD11c cells isolated from the PPs of P-Fag e 2-fed mice.

CONCLUSION

These results indicate that attenuated allergens can suppress Th2-induced allergic responses via induction of Tfh cells, which are regulated by IL-6 secreted from dendritic cells.

摘要

范围

荞麦是亚洲国家常见的食物过敏原,其中荞麦过敏原 1(Fag e 1)和荞麦过敏原 2(Fag e 2)是主要的过敏原。本研究旨在通过磷酸化来减弱这些过敏原,从而制备一种口服免疫治疗剂。评估了磷酸化荞麦过敏原 2(P-Fag e 2)在荞麦过敏小鼠模型中的免疫调节作用。

方法和结果

通过在存在焦磷酸盐的情况下干热制备磷酸化 Fag e 1(P-Fag e 1)和 P-Fag e 2。随后使用食物过敏患者的血清进行斑点印迹分析表明,两种蛋白质在磷酸化后均表现出降低的变应原性。与假处理的小鼠相比,经 P-Fag e 2 口服给药 6 周的小鼠在 Fag e 2 致敏后表现出特异性血清 IgE 降低和特异性 IgA 增加。此外,磷酸化抗原喂养的小鼠的派尔氏斑(PP)显示 IL-4 产生减少和滤泡辅助性 T 细胞(Tfh)细胞的诱导。从 P-Fag e 2 喂养的小鼠的 PP 中分离出的 CD11c 细胞中观察到 IL-6 的产生增加。

结论

这些结果表明,减弱的过敏原可以通过诱导 Tfh 细胞来抑制 Th2 诱导的过敏反应,而 Tfh 细胞受树突状细胞分泌的 IL-6 调节。

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