Sunil K Ahuja1, Muthu Saravanan Manoharan2, Nathan L Harper3, Fabio Jimenez3, Benjamin D Hobson4, Hernan Martinez3, Puraskar Ingale2, Ya-Guang Liu2, Andrew Carrillo2, Zheng Lou2, Dean L Kellog2, Seema S Ahuja2, Cynthia G Rather5, Robert E Esch6, Daniel A Ramirez5, Robert A Clark2, Kari Nadeau7, Charles P Andrews5, Robert L Jacobs5, Weijing He2. 1. Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, University of Texas Health Science Center, San Antonio, Tex; Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Tex; Department of Biochemistry, University of Texas Health Science Center, San Antonio, Tex. Electronic address: ahujas@uthscsa.edu. 2. Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, University of Texas Health Science Center, San Antonio, Tex. 3. Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Tex; Department of Medicine, University of Texas Health Science Center, San Antonio, Tex; Foundation for Advancing Veterans' Health Research, San Antonio, Tex. 4. Department of Pediatrics, School of Medicine, Stanford University, Stanford, Calif; Sean N. Parker Center for Allergy Research, School of Medicine, Stanford University, Stanford, Calif. 5. Biogenics Research Chamber, San Antonio, Tex. 6. School of Natural Sciences, Lenoir-Rhyne University, Hickory, NC. 7. Department of Pediatrics, School of Medicine, Stanford University, Stanford, Calif; Sean N. Parker Center for Allergy Research, School of Medicine, Stanford University, Stanford, Calif; Division of Allergy, Immunology, and Rheumatology, Lucile Packard Children's Hospital at Stanford Hospital, Stanford, Calif.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
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