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A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility.
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2020-01-17 , DOI: 10.1016/j.jaci.2019.12.912
Akila Rekima 1 , Chrystelle Bonnart 2 , Patricia Macchiaverni 1 , Jessica Metcalfe 3 , Meri K Tulic 4 , Nicolas Halloin 5 , Samah Rekima 6 , Jon Genuneit 7 , Samantha Zanelli 5 , Samara Medeiros 8 , Debra J Palmer 9 , Susan Prescott 10 , Valerie Verhasselt 11
Affiliation  

BACKGROUND Successful prevention of food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to food antigen in early life. OBJECTIVES This study sought to determine whether oral exposure to Dermatophagoides pteronyssinus through breast milk affects gut mucosal immunity with long-term effects on IgE-mediated food allergy susceptibility. METHODS Gut immunity was explored in 2-week-old mice breast-fed by mothers exposed to D pteronyssinus, protease-inactivated D pteronyssinus, or to PBS during lactation. We further analyzed oral tolerance to a bystander food allergen, ovalbumin (OVA). In a proof-of-concept study, Der p 1 and OVA levels were determined in 100 human breast milk samples and the association with prevalence of IgE-mediated egg allergy at 1 year was assessed. RESULTS Increased permeability, IL-33 levels, type 2 innate lymphoid cell activation, and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to D pteronyssinus compared with PBS. This pro-Th2 gut mucosal environment inhibited the induction of antigen-specific FoxP3 regulatory T cells and the prevention of food allergy by OVA exposure through breast milk. In contrast, protease-inactivated D pteronyssinus had no effect on offspring gut mucosal immunity. Based on the presence of Der p 1 and/or OVA in human breast milk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk. CONCLUSIONS This study highlights an unpredicted potential risk factor for the development of food allergy, that is, D pteronyssinus allergens in breast milk, which disrupt gut immune homeostasis and prevents oral tolerance induction to bystander food antigen through their protease activity.

中文翻译:

早期口服通过母乳接触屋尘螨过敏原在IgE介导的食物过敏易感性中起作用。

背景技术成功地预防食物过敏需要识别不利影响早期生命发展对食物抗原的口服耐受性的能力的因素。目的本研究旨在确定通过母乳口服暴露于翼龙皮的皮肤是否会影响肠道粘膜免疫,并对IgE介导的食物过敏易感性产生长期影响。方法在母乳喂养的2周龄小鼠中,研究了其母乳喂养的情况,这些母乳暴露于D蕨类植物,蛋白酶灭活的D蕨类植物或哺乳期的PBS中。我们进一步分析了对旁观者食物过敏原卵清蛋白(OVA)的口服耐受性。在概念验证研究中,确定了100份人类母乳样品中的Der p 1和OVA水平,并评估了1年时IgE介导的鸡蛋过敏的患病率。结果与暴露于PBS的母亲相比,在暴露于D型翼龙的母亲哺育的小鼠的肠粘膜中发现通透性,IL-33水平,2型先天淋巴样细胞活化和Th2细胞分化增加。这种亲Th2肠粘膜环境通过母乳中的OVA暴露抑制了抗原特异性FoxP3调节性T细胞的诱导和食物过敏的预防。相比之下,蛋白酶灭活的D蕨类植物对后代肠道粘膜免疫没有影响。根据人母乳中Der p 1和/或OVA的存在,我们确定了哺乳期母亲的群体,这与在小鼠中发现的造成不同鸡蛋过敏风险的母婴相似。结论本研究强调了食物过敏发展的不可预测的潜在危险因素,即母乳中的D蕨类植物过敏原,
更新日期:2020-01-17
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