Preservation of epithelial cell barrier function and muted inflammation in resistance to allergic rhinoconjunctivitis from house dust mite challenge - 19/04/17
, Muthu Saravanan Manoharan, MS a, b, ∗, Nathan L. Harper, MS a, b, e, ∗, Fabio Jimenez, MS a, b, e, Benjamin D. Hobson, BS f, g, Hernan Martinez, MD a, b, e, Puraskar Ingale, MS a, b, Ya-Guang Liu, MD, PhD a, b, Andrew Carrillo, BS a, b, Zheng Lou, PhD a, b, Dean L. Kellog, BS a, b, Seema S. Ahuja, MD a, b, Cynthia G. Rather, CCRC h, Robert E. Esch, PhD i, Daniel A. Ramirez, MD h, Robert A. Clark, MD a, b, Kari Nadeau, MD, PhD f, g, j, Charles P. Andrews, MD h, Robert L. Jacobs, MD h, Weijing He, MD a, bAbstract |
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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Allergen challenge chamber, house dust mites, rhinoconjunctivitis, RNA sequencing, epithelial barrier
Abbreviations used : ACC, AR, CyTOF, GO, GWAS, HDM, M+, M−, RNA-seq, TSS
Mappa
| Supported by a the Doris Duke Distinguished Clinical Scientist Award, a Burroughs Wellcome Clinical Scientist in Transitional Research Award, a Max and Minnie Tomerlin Senior Scholar Voelcker Award, and a grant from the Center for Personalized Medicine (CX00875-01A1) at the South Texas Veterans Health Care System (S.K.A.); by a National Institutes of Health Clinical and Translational Science Award (UL1-TR001120; R.A.C.); and by the Sean N. Parker Center for Food Allergy Research (K.N.). |
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| Disclosures and potential conflicts of interest: R. L. Jacobs, C. P. Andrews, and D. A. Ramirez are co-owners of Biogenics Research Chamber. C. G. Rather is executive director of Chamber Operations at Biogenics Research Chamber. R. E. Esch was employed by Greer Laboratories at time of these studies. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 3
P. 844-854 - marzo 2017 Ritorno al numero
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