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

• Published in: Journal of allergy and clinical immunology Vol. 139; no. 3; pp. 844 - 854
• Main Authors: Ahuja, Sunil K., MD, Manoharan, Muthu Saravanan, MS, Harper, Nathan L., MS, Jimenez, Fabio, MS, Hobson, Benjamin D., BS, Martinez, Hernan, MD, Ingale, Puraskar, MS, Liu, Ya-Guang, MD, PhD, Carrillo, Andrew, BS, Lou, Zheng, PhD, Kellog, Dean L., BS, Ahuja, Seema S., MD, Rather, Cynthia G., CCRC, Esch, Robert E., PhD, Ramirez, Daniel A., MD, Clark, Robert A., MD, Nadeau, Kari, MD, PhD, Andrews, Charles P., MD, Jacobs, Robert L., MD, He, Weijing, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017; Elsevier Limited
• Subjects: Administration, Inhalation; Adult; Allergen challenge chamber; Allergens - immunology; Allergy and Immunology; Animals; Antigens, Dermatophagoides - immunology; Blood; Conjunctivitis, Allergic - genetics; Conjunctivitis, Allergic - immunology; Dermatophagoides pteronyssinus; Disease Resistance; epithelial barrier; Epithelial Cells - immunology; Epithelial Cells - metabolism; Female; Flow cytometry; Food allergies; Gene expression; Genomes; house dust mites; Humans; Hypotheses; Inflammation; Leukocyte Count; Male; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Preservation; Pyroglyphidae - immunology; Rhinitis, Allergic - genetics; Rhinitis, Allergic - immunology; rhinoconjunctivitis; RNA sequencing; Studies; Transcriptome; RNA sequencing; ACC; HDM sensitized; Genome-wide association studies; GWAS; Allergic rhinoconjunctivitis; GO; House dust mite; M; house dust mites; rhinoconjunctivitis; Gene ontology; HDM; Total symptom score; AR; Allergen challenge chamber; HDM nonsensitized; epithelial barrier; RNA-seq; TSS; Time-of-flight mass cytometry; CyTOF
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2016.08.019

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.