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No evidence for IgE receptor FcεRI expression on bronchial epithelial cells of asthmatic patients

1 Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada
2 Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB
3 MBRU, Dubai, United Arab Emirates
4 College of Medicine, University of Sharjah, Sharjah, United Arab Emirates

Immunoglobulin E (IgE) plays an important role in the pathogenesis of asthma and anti-IgE therapy was approved for treating patients with severe persistent allergic asthma. The exact target sites of anti-IgE therapy are not well characterized; however, it has been proposed that the therapeutic effects of anti-IgE come from its intervention in the airway remodeling process. To gain insights on how anti-IgE therapy improves asthma symptoms, we aimed to validate the expression of FcεRI on airway epithelial cells and demonstrate its role in airway remodeling. The expression of FcεRI was measured (1) in situ in bronchial biopsy tissues of asthmatic and control subjects using immunohistochemistry and (2) in vitro in primary bronchial epithelial cells obtained from asthmatic subjects, at baseline and after treatment with human IgE, using qPCR and flow cytometry. FcεRI expression in situ was detected only in a very small number of cells in the epithelium of bronchial biopsies of asthmatic and control subjects. In vitro measurement revealed no expression of the receptor both at baseline and after stimulation with IgE. The release of transforming growth factor—beta (TGF)-β and thymic stromal lymphopoietin (TSLP) were examined by ELISA in bronchial epithelial cells after crosslinking of IgE. No significant differences in TSLP and TGF-β protein levels were detected between stimulated and unstimulated cells. Hence, our data conclusively indicate that bronchial epithelial cells have negligible expression of functional high affinity receptor for IgE. Taken together, anti-IgE therapy is very likely to exert its therapeutic effects via other structural cell types.
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Keywords immunoglobulin E; high-affinity receptor FcεRI; severe asthma; airway inflammation; airway remodeling

Citation: Omer Qibi, Severine Audusseau, Andrea Mogas, Zoulfia Allakhverdi, Abdelilah Soussi Gounni, Saba Al Heialy, Qutayba Hamid. No evidence for IgE receptor FcεRI expression on bronchial epithelial cells of asthmatic patients. AIMS Allergy and Immunology, 2018, 2(4): 165-179. doi: 10.3934/Allergy.2018.4.165


  • 1. Galli SJ, Tsai M, Piliponsky AM (2008) The development of allergic inflammation. Nature 454: 445–454.    
  • 2. James AL, Wenzel S (2007) Clinical relevance of airway remodelling in airway diseases. Eur Respir J 30: 134–155.    
  • 3. Sumi Y, Hamid Q (2007) Airway remodeling in asthma. Allergol Int 56: 341–348.    
  • 4. Crimi E, Scordamaglia A, Crimi P, et al. (1983) Total and specific IgE in serum, bronchial lavage and bronchoalveolar lavage of asthmatic patients. Allergy 38: 553–559.    
  • 5. Platts-Mills TA (2001) The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med 164: S1–S5.    
  • 6. Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8: 205–217.    
  • 7. Holgate S, Casale T, Wenzel S, et al. (2005) The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol 115: 459–465.    
  • 8. Humbert M, Busse W, Hanania NA, et al. (2014) Omalizumab in asthma: An update on recent developments. J Allergy Clin Immunol Pract 2: 525–536.    
  • 9. Holowka D, Sil D, Torigoe C, et al. (2007) Insights into immunoglobulin E receptor signaling from structurally defined ligands. Immunol Rev 217: 269–279.    
  • 10. Kraft S, Kinet JP (2007) New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 7: 365–378.    
  • 11. Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18: 693–704.    
  • 12. Maurer D, Fiebiger S, Ebner C, et al. (1996) Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation. J Immunol 157: 607–616.
  • 13. Redhu NS, Gounni AS (2013) The high affinity IgE receptor (FcepsilonRI) expression and function in airway smooth muscle. Pulm Pharmacol Ther 26: 86–94.    
  • 14. Untersmayr E, Bises G, Starkl P, et al. (2010) The high affinity IgE receptor Fc epsilonRI is expressed by human intestinal epithelial cells. PLoS One 5: e9023.    
  • 15. Yokota A, Kikutani H, Tanaka T, et al. (1988) Two species of human Fc epsilon receptor II (Fc epsilon RII/CD23): Tissue-specific and IL-4-specific regulation of gene expression. Cell 55: 611–618.    
  • 16. Foster B, Metcalfe DD, Prussin C (2003) Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: Correlation with serum IgE and allergic asthma. J Allergy Clin Immunol 112: 1132–1138.    
  • 17. Sihra BS, Kon OM, Grant JA, et al. (1997) Expression of high-affinity IgE receptors (Fc epsilon RI) on peripheral blood basophils, monocytes, and eosinophils in atopic and nonatopic subjects: Relationship to total serum IgE concentrations. J Allergy Clin Immunol 99: 699–706.    
  • 18. Malveaux FJ, Conroy MC, Jr AN, et al. (1978) IgE receptors on human basophils. Relationship to serum IgE concentration. J Clin Invest 62: 176–181.
  • 19. Nopp A, Johansson SG, Adedoyin J, et al. (2010) After 6 years with Xolair; a 3-year withdrawal follow-up. Allergy 65: 56–60.    
  • 20. Molimard M, Mala L, Bourdeix I, et al. (2014) Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control. Respir Med 108: 571–576.    
  • 21. Roth M, Zhong J, Zumkeller C, et al. (2013) The role of IgE-receptors in IgE-dependent airway smooth muscle cell remodelling. PLoS One 8: e56015.    
  • 22. Campbell AM, Vachier I, Chanez P, et al. (1998) Expression of the high-affinity receptor for IgE on bronchial epithelial cells of asthmatics. Am J Respir Cell Mol Biol 19: 92–97.    
  • 23. Takhar P, Corrigan CJ, Smurthwaite L, et al. (2007) Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. J Allergy Clin Immunol 119: 213–218.    
  • 24. Bajpai R, Lesperance J, Kim M, et al. (2008) Efficient propagation of single cells accutase-dissociated human embryonic stem cells. Mol Reprod Dev 75: 818–827.    
  • 25. Furuichi K, Rivera J, Isersky C (1985) The receptor for immunoglobulin E on rat basophilic leukemia cells: Effect of ligand binding on receptor expression. Proc Natl Acad Sci USA 82: 1522–1525.    
  • 26. Gebhardt T, Lorentz A, Detmer F, et al. (2005) Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1. Gut 54: 928–934.    
  • 27. Gomez G, Ramirez CD, Rivera J, et al. (2005) TGF-beta 1 inhibits mast cell Fc epsilon RI expression. J Immunol 174: 5987–5993.    
  • 28. Okayama Y, Okumura S, Sagara H, et al. (2009) FcepsilonRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells. Eur Respir J 34: 425–435.    
  • 29. Corren J, Kavati A, Ortiz B, et al. (2018) Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with omalizumab: A systematic literature review of randomized controlled trials. Curr Med Res Opin 34: 65–80.    
  • 30. Jr MGD, Bochner BS, Adelman DC, et al. (1997) Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 158: 1438–1445.
  • 31. Djukanovic R, Wilson SJ, Kraft M, et al. (2004) Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med 170: 583–593.    
  • 32. Prussin C, Griffith DT, Boesel KM, et al. (2003) Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 112: 1147–1154.    
  • 33. Huang YC, Leyko B, Frieri M (2005) Effects of omalizumab and budesonide on markers of inflammation in human bronchial epithelial cells. Ann Allergy Asthma Immunol 95: 443–451.    
  • 34. Gounni AS, Wellemans V, Yang J, et al. (2005) Human airway smooth muscle cells express the high affinity receptor for IgE (Fc epsilon RI): A critical role of Fc epsilon RI in human airway smooth muscle cell function. J Immunol 175: 2613–2621.    
  • 35. Roth M, Tamm M (2010) The effects of omalizumab on IgE-induced cytokine synthesis by asthmatic airway smooth muscle cells. Ann Allergy Asthma Immunol 104: 152–160.    
  • 36. Hoshino M, Ohtawa J (2012) Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration 83: 520–528.    
  • 37. Tajiri T, Niimi A, Matsumoto H, et al. (2014) Comprehensive efficacy of omalizumab for severe refractory asthma: A time-series observational study. Ann Allergy Asthma Immunol 113: 470–475.    
  • 38. Saglani S, Payne DN, Zhu J, et al. (2007) Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med 176: 858–864.    
  • 39. Grainge CL, Lau LC, Ward JA, et al. (2011) Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 364: 2006–2015.    
  • 40. Borkowski TA, Jouvin MH, Lin SY, et al. (2001) Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI. J Immunol 167: 1290–1296.    
  • 41. Campbell AM, Vignola AM, Chanez P, et al. (1994) Low-affinity receptor for IgE on human bronchial epithelial cells in asthma. Immunology 82: 506–508.
  • 42. Palaniyandi S, Tomei E, Li Z, et al. (2011) CD23-dependent transcytosis of IgE and immune complex across the polarized human respiratory epithelial cells. J Immunol 186: 3484–3496.    
  • 43. Mauri P, Riccio AM, Rossi R, et al. (2014) Proteomics of bronchial biopsies: Galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients. Immunol Lett 162: 2–10.    


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