Nasal epithelial barrier dysfunction increases sensitization and mast cell degranulation in the absence of allergic inflammation

Allergy: European Journal of Allergy and Clinical Immunology - Tập 75 Số 5 - Trang 1155-1164 - 2020
Inge Kortekaas Krohn1, Sven Seys1,2, G. Lund3, Anne‐Charlotte Jonckheere1, Isabelle Dierckx de Casterlé1, Jan Ceuppens1, Brecht Steelant1, Peter W. Hellings4,5,6
1Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium
2European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Brussels, Belgium
3ALK Abello, Hørsholm, Denmark
4Clinical Division of Otorhinolaryngology, Head and Neck Surgery, Academic Medical Center, Amsterdam, The Netherlands
5Clinical Division of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium
6Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium

Tóm tắt

AbstractBackgroundIncreased epithelial permeability has been reported in allergic rhinitis, with histamine and type‐2 inflammation being responsible for tight junction dysfunction. The impact of an epithelial barrier defect on allergic sensitization and mast cell (MC) degranulation remains speculative.MethodsTransepithelial passage of allergens was evaluated on primary human nasal epithelial cell cultures. Active sensitization was attempted by repeated intranasal ovalbumin (OVA) applications in Naïve mice. In a passive sensitization model, mice were injected with IgE to Dermatophagoides pteronyssinus (rDer p)2 and then exposed intranasally to the allergen. Chitosan was used to disrupt nasal epithelial integrity in vitro and in vivo.ResultsChitosan strongly reduced transepithelial electrical resistance and facilitated transepithelial allergen passage in cultured primary nasal epithelial cells. In vivo, intranasal chitosan affected occludin expression and facilitated allergen passage. After epithelial barrier disruption, intranasal OVA application induced higher OVA‐specific IgG1 and total IgE in serum, and increased eosinophilia and interleukin‐5 in bronchoalveolar lavage (BAL) compared to sham‐OVA mice. Chitosan exposure, prior to rDer p2 allergen challenge in passively sensitized mice, resulted in increased β‐hexosaminidase levels in serum and BAL compared to sham‐rDer p2 mice. Intranasal treatment with the synthetic glucocorticoid fluticasone propionate prevented chitosan‐induced barrier dysfunction, allergic sensitization, and MC degranulation.ConclusionEpithelial barrier dysfunction facilitates transepithelial allergen passage, allergic sensitization, and allergen‐induced MC degranulation even in the absence of inflammatory environment. These results emphasize the crucial role of an intact epithelial barrier in prevention of allergy.

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Allergy: European Journal of Allergy and Clinical Immunology

Tập 75 Số 5

1155-1164

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