The role of immunoglobulin E in airway remodeling in asthma

ABSTRACTImmunoglobulin E (IgE) plays an important role in the pathogenesis of asthma, a chronic disease of the airways characterized often by inflammation and remodeling. In a large proportion of asthmatic patients, anti-IgE therapy is effective in controlling their symptoms. The exact target sites of anti-IgE are not well characterized; however, it has been proposed that the therapeutic effects of anti-IgE come from its intervention of the inflammation and airway remodeling process. IgE acts on two types of receptors: a high affinity receptor and a low affinity receptor. The high affinity receptor or Fc epsilon RI (FceRI), has been reported to express on inflammatory cells such as mast cells, basophils and eosinophils. An allergen, upon re-exposure, cross-links the membrane bound IgE-receptor complex and leads to the degranulation and release of mediators including histamine and prostaglandins, which in turn drive airway inflammation in asthma. In addition to inflammatory cells, FceRI has also been reported to express on airway structural cells such as airway smooth muscle cells, where it enhances the production of extracellular matrix (ECM) proteins, proliferation of airway smooth muscle cells (ASMC) and release of cytokines. Airway epithelial cells are involved in the remodeling process by producing remodeling associated cytokines such as transforming growth factor–beta (TGF)-β and thymic stromal lymphopoietin (TSLP). Although FceRI has also been reported to express on airway epithelial cells, the findings are elusive. To gain an insight on how anti-IgE therapy improves asthma symptoms, in this study we aimed to validate the expression of FceRI on airway epithelial cells and demonstrate its role in airway remodeling. We measured the expression of FceRI (1) in situ in bronchial biopsy tissues of asthmatic and control subjects using immunohistochemistry and (2) in vitro in primary human bronchial epithelial cells obtained from asthmatic subjects, at baseline and after treatment with human IgE, using qPCR and flow cytometry. FceRI 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 treatment with IgE. To convincingly conclude the absence of FceRI in bronchial epithelial cells, we incubated cells with crosslinking antibody and examined the downstream effects of IgE (i.e. the release of TSLP and TGF-β cytokines) using ELISA. No significant difference in TSLP and TGF-β protein releases was detected between stimulated and unstimulated cells. Hence, our data conclusively indicated that bronchial epithelial cells do not express functional high affinity receptor for IgE. Anti-IgE is therefore likely to exert its therapeutic effects via other structural cell types.%%%%RESUMEL'immunoglobuline E (IgE) joue un role important dans la pathogenese de l'asthme, une maladie chronique des voies respiratoires souvent caracterisee par l'inflammation et le…