Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge
Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge
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DOI：
10.1016/j.jaci.2016.08.019
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发表时间：
2017-03-01
影响因子：
14.2
通讯作者：
He, Weijing
中科院分区：
文献类型：
--
作者：
Ahuja, Sunil K.;Manoharan, Muthu Saravanan;He, Weijing
背景资料：一个新兴的范例认为，对过敏性疾病（包括过敏性鼻结膜炎）发展的抵抗力与儿童早期完整的上皮/表皮屏障有关。可以想象，这种耐药性的免疫学和基因组足迹在非特应性、非过敏性成人中得以保留，并且在暴露于空气allergene.Objective：本研究的目的是获得对过敏性鼻结膜炎上皮/表皮屏障模型的直接支持。23名成年人对屋尘螨（HDM）（M+）过敏，15名成年人不敏感，非过敏性（M-）参与者在过敏原激发室中连续4天完成对雾化HDM（屋尘螨）粉末的3小时暴露。我们分析：结果：在HDM攻击中：（1）只有M+个体出现过敏性鼻结膜炎症状;（2）M+和M-个体的外周血白细胞水平/应答和鼻细胞基因表达模式基本一致;在基线（暴露前）未观察到这些参数的总体差异。观察到两个关键差异。首先，外周血CD 4（+）和CD 8（+）T细胞活化水平最初在M-参与者中降低，而在M+参与者中升高。第二，与M+参与者相比，在M-中，促进表皮/上皮屏障功能的基因（例如，细丝聚集蛋白[丝聚蛋白]）与炎症（如趋化因子）和先天免疫（干扰素）分别上调和减弱。在非特应性中对HDM攻击的抗性的印记，在非过敏性成人中，外周血中的T细胞活化和鼻室中的炎症反应减弱，加上促进表皮/上皮细胞屏障功能的基因上调。
Background: An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis, relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen.Objective: The aim of this study was to obtain direct support of the epithelial/epidermal barrier model for allergic rhinoconjunctivitis.Methods: Twenty-three adults allergic to house dust mites (HDMs) (M+) and 15 nonsensitive, nonallergic (M-) participants completed 3-hour exposures to aerosolized HDM (Dermatophagoides pteronyssinus) powder on 4 consecutive days in an allergen challenge chamber. We analyzed: (1) peripheral blood leukocyte levels and immune responses; and (2) RNA sequencing-derived expression profiles of nasal cells, before and after HDM exposure.Results: On HDM challenge: (1) onlyM+ persons developed allergic rhinoconjunctivitis symptoms; and (2) peripheral blood leukocyte levels/responses and gene expression patterns in nasal cells were largely concordant between M+ and M- participants; gross differences in these parameters were not observed at baseline (pre-exposure). Two key differences were observed. First, peripheral blood CD4(+) and CD8(+) T-cell activation levels initially decreased in M- participants versus increased in M+ participants. Second, in M-compared with M+ participants, genes that promoted epidermal/epithelial barrier function (eg, filament- aggregating protein [filaggrin]) versus inflammation (eg, chemokines) and innate immunity (interferon) were upregulated versus muted, respectively.Conclusion: An imprint of resistance to HDM challenge in nonatopic, nonallergic adults was muted T-cell activation in the peripheral blood and inflammatory response in the nasal compartment, coupled with upregulation of genes that promote epidermal/epithelial cell barrier function.