期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 139, 期 3, 页码 844-854出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.08.019
关键词
Allergen challenge chamber; house dust mites; rhino-conjunctivitis; RNA sequencing; epithelial barrier
资金
- Doris Duke Distinguished Clinical Scientist Award
- Burroughs Wellcome Clinical Scientist in Transitional Research Award
- Max and Minnie Tomerlin Senior Scholar Voelcker Award
- Center for Personalized Medicine South Texas Veterans Health Care System [CX00875-01A1]
- National Institutes of Health Clinical and Translational Science Award [UL1-TR001120]
- Sean N. Parker Center for Food Allergy Research
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.
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