title: Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
authors.affiliation: 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.
authors.forename: Muthu Saravanan
authors.initials: MS
authors.lastname: Manoharan
authors.affiliation: 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.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Harper
authors.affiliation: 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.
authors.forename: Fabio
authors.initials: F
authors.lastname: Jimenez
authors.affiliation: Department of Pediatrics, School of Medicine, Stanford University, Stanford, Calif; Sean N. Parker Center for Allergy Research, School of Medicine, Stanford University, Stanford, Calif.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hobson
authors.affiliation: 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.
authors.forename: Hernan
authors.initials: H
authors.lastname: Martinez
authors.affiliation: 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.
authors.forename: Puraskar
authors.initials: P
authors.lastname: Ingale
authors.affiliation: 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.
authors.forename: Ya-Guang
authors.initials: YG
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carrillo
authors.affiliation: 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lou
authors.affiliation: 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.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Kellog
authors.affiliation: 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.
authors.forename: Seema S
authors.initials: SS
authors.lastname: Ahuja
authors.affiliation: Biogenics Research Chamber, San Antonio, Tex.
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Rather
authors.affiliation: School of Natural Sciences, Lenoir-Rhyne University, Hickory, NC.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Esch
authors.affiliation: Biogenics Research Chamber, San Antonio, Tex.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ramirez
authors.affiliation: 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.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.affiliation: 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.
authors.forename: Kari
authors.initials: K
authors.lastname: Nadeau
authors.affiliation: Biogenics Research Chamber, San Antonio, Tex.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Andrews
authors.affiliation: Biogenics Research Chamber, San Antonio, Tex.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jacobs
authors.affiliation: 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.
authors.forename: Weijing
authors.initials: W
authors.lastname: He
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000235:genetics / Q000276:immunology*; D060467:Disease Resistance; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology*; D059467:Transcriptome
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; C000717249:FLG protein, human; D000091344:Filaggrin Proteins
keywords: Allergen challenge chamber; RNA sequencing; epithelial barrier; house dust mites; rhinoconjunctivitis