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

Sunil K Ahuja, Muthu Saravanan Manoharan, Nathan L. Harper, Fabio Jimenez, Benjamin D. Hobson, Hernan Martinez, Puraskar Ingale, Ya-guang Liu, Andrew Carrillo, Zheng Lou, Dean L. Kellog, Seema S Ahuja, Cynthia G. Rather, Robert E. Esch, Daniel A. Ramirez, Robert A Clark, Kari Nadeau, Charles P. Andrews, Robert L. Jacobs, Weijing He

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Abstract

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) only M+ 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.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
Publication statusAccepted/In press - Oct 27 2014

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Keywords

  • Allergen challenge chamber
  • Epithelial barrier
  • House dust mites
  • Rhinoconjunctivitis
  • RNA sequencing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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