Histamine and T helper cytokine–driven epithelial barrier dysfunction in allergic rhinitis - 07/03/18
Abstract |
Background |
Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and TH2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier.
Objective |
We sought to investigate the role of histamine and TH2 cells in driving epithelial barrier dysfunction in AR.
Methods |
Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4 kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested in vitro. In addition, the effect of activated TH1 and TH2 cells, mast cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-γ, and TNF-α on mucosal permeability was tested in vivo.
Results |
Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated TH1 and TH2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the TH1- and TH2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ, and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation.
Conclusions |
Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Allergic rhinitis, idiopathic rhinitis, tight junctions, histamine, TH2 cells, primary nasal epithelial cells
Abbreviations used : ALI, AR, BAL, FD4, HDM, IR, KU, pNEC, TER, TGN, TJ, ZO
Plan
| The authors' laboratories are supported by grants from the Belgian Federal Government (IUAP P7/30), Innovatie door Wetenschap en Technologie (IWT) (TBM project 130260), and the research council of the KU Leuven (GOA 2009/07 and 14/011). This work was partly supported by a research grant of the Fund of Scientific Research (FWO), Flanders, Belgium. P.W.H. and D.M.B. are recipients of a senior researcher fellowship from FWO. S.F.S. is supported by the research council of KU Leuven (PDMK/14/189). |
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| Disclosure of potential conflict of interest: B. Steelant's institution received grants from Belgian Federal Government (IUAP P7/30), IWT (TBM 130260), KU Leuven Research Council (GOA 2009/07), and KU Leuven Research Council (GOA 14/011) for this work. S. Seys' institute received grants from Research Foundation Flanders for other works; personally received payment for lectures from Meda Pharma. M. Van Woensel's institute received grant 121206 from IWT Vlaanderen for this work. I. Kortekaas Krohn's institution received grants from IWT (project 130260) and the Research Council of KU Leuven (2009/07 and 14/011) for this work. D. Bullens' institution received consultancy fees from Hong Kong Research Grants Council and grants from FWO-TBM project grant pending and travel expenses from travel and stay EAACI Helsinki 2017 (ALK); EAACI Barcelona 2016 (Hal Allergy) for other works; personally received consultancy fees from FNRS grant revision. C. A. Akdis received grants from Actelion, EU FP 7 Projects Medall and Predicta, Allergopharma, Swiss National Science Foundation, and Christine Kühne Center for Allergy Research and Education for other works. J. Ceuppens's institution received grants from Circassia and ASIT Biotec for other works; personally received consultancy fees from Pfizer; personally received payment for lectures from Novartis; and travel expenses from Pfizer. All of the other authors state they have no conflict of interest. |
Vol 141 - N° 3
P. 951 - mars 2018 Retour au numéro
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