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

Research output: Contribution to journalArticle

8 Scopus citations

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)
Pages (from-to)844-854
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number3
DOIs
StatePublished - Mar 2017

Keywords

  • Allergen challenge chamber
  • RNA sequencing
  • epithelial barrier
  • house dust mites
  • rhinoconjunctivitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ahuja, S. K., Manoharan, M. S., Harper, N. L., Jimenez, F., Hobson, B. D., Martinez, H., Ingale, P., Liu, Y. G., Carrillo, A., Lou, Z., Kellog, D. L., Ahuja, S. S., Rather, C. G., Esch, R. E., Ramirez, D. A., Clark, R. A., Nadeau, K., Andrews, C. P., Jacobs, R. L., & He, W. (2017). Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge. Journal of Allergy and Clinical Immunology, 139(3), 844-854. https://doi.org/10.1016/j.jaci.2016.08.019