Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge.

An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis (AR), 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.To obtain direct support of the epithelial/epidermal barrier model for AR.Twenty-three adults allergic to house dust mites (HDM; 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 (ACC). We analyzed (1) peripheral blood leukocyte levels and immune responses and (2) RNA-seq-derived expression profiles of nasal cells, before and after HDM exposure.During HDM challenge (1) only M+ persons developed AR 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- vs increased in M+ participants. Second, in M- compared with M+ participants, genes that promoted epidermal/epithelial barrier function (e.g., filaggrin) vs. inflammation (e.g., chemokines) and innate immunity (interferon) were upregulated vs. muted, respectively.An imprint of resistance to HDM challenge in nonatopic, nonallergic adults was muted T-cell activation and inflammatory responses in the peripheral blood and nasal compartment, respectively, coupled with upregulation of genes that promote epidermal/epithelial cell barrier function.