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

7 Citations (Scopus)

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
StateAccepted/In press - Oct 27 2014

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Pyroglyphidae
Epithelial Cells
Inflammation
Nose
Leukocytes
Dermatophagoides pteronyssinus
RNA Sequence Analysis
T-Lymphocytes
Chemokines
Innate Immunity
Powders
Allergens
Interferons
Genes
Up-Regulation
Gene Expression
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge. / Ahuja, Sunil K; Manoharan, Muthu Saravanan; Harper, Nathan L.; Jimenez, Fabio; Hobson, Benjamin D.; Martinez, Hernan; Ingale, Puraskar; Liu, Ya-guang; Carrillo, Andrew; Lou, Zheng; Kellog, Dean L.; Ahuja, Seema S; Rather, Cynthia G.; Esch, Robert E.; Ramirez, Daniel A.; Clark, Robert A; Nadeau, Kari; Andrews, Charles P.; Jacobs, Robert L.; He, Weijing.

In: Journal of Allergy and Clinical Immunology, 27.10.2014.

Research output: Contribution to journalArticle

Ahuja, SK, Manoharan, MS, Harper, NL, Jimenez, F, Hobson, BD, Martinez, H, Ingale, P, Liu, Y, Carrillo, A, Lou, Z, Kellog, DL, Ahuja, SS, Rather, CG, Esch, RE, Ramirez, DA, Clark, RA, Nadeau, K, Andrews, CP, Jacobs, RL & He, W 2014, '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. https://doi.org/10.1016/j.jaci.2016.08.019
Ahuja, Sunil K ; Manoharan, Muthu Saravanan ; Harper, Nathan L. ; Jimenez, Fabio ; Hobson, Benjamin D. ; Martinez, Hernan ; Ingale, Puraskar ; Liu, Ya-guang ; Carrillo, Andrew ; Lou, Zheng ; Kellog, Dean L. ; Ahuja, Seema S ; Rather, Cynthia G. ; Esch, Robert E. ; Ramirez, Daniel A. ; Clark, Robert A ; Nadeau, Kari ; Andrews, Charles P. ; Jacobs, Robert L. ; He, Weijing. / Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge. In: Journal of Allergy and Clinical Immunology. 2014.
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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.",
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AU - Ahuja, Sunil K

AU - Manoharan, Muthu Saravanan

AU - Harper, Nathan L.

AU - Jimenez, Fabio

AU - Hobson, Benjamin D.

AU - Martinez, Hernan

AU - Ingale, Puraskar

AU - Liu, Ya-guang

AU - Carrillo, Andrew

AU - Lou, Zheng

AU - Kellog, Dean L.

AU - Ahuja, Seema S

AU - Rather, Cynthia G.

AU - Esch, Robert E.

AU - Ramirez, Daniel A.

AU - Clark, Robert A

AU - Nadeau, Kari

AU - Andrews, Charles P.

AU - Jacobs, Robert L.

AU - He, Weijing

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N2 - 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.

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