The role of E-cadherin/β-catenin signalling in the development of an asthmatic airway epithelial phenotype

Asthma is a chronic inflammatory disease broadly characterised by symptoms such as coughing, wheezing, and tightness of chest. These symptoms are caused by aberrant airway remodelling and reversible airway obstruction and hyperresponsiveness of the airways to inhaled allergens like house dust mite (HDM) and grass or tree pollen or to environmental stimuli like tobacco smoke and air pollution. Around 1000 people die every day due to asthma and more than 300 million are currently suffering from the disease worldwide (1). Allergen-induced asthma or atopic asthma is the most common type of asthma, described by elevated serum Immunoglobulin (Ig) E, T helper 2 (Th2) cell mediated airway inflammation and airway remodelling. Th2 cells release cytokines IL-4, IL-5, IL-9 and IL-13 that induce IgE production by B-lymphocytes, eosinophilic infiltration into the airways and goblet cell hyperplasia with excessive mucus production (2). IgE antibodies bind to mast cells, which can trigger the release of histamine, leukotrienes, and prostaglandins after IgE crosslinking, resulting in airway obstruction due to excessive smooth muscle contraction, mucosal swelling, and mucus production (2). Early childhood exposure to allergens resulting in allergic sensitisation increases the risk of atopic asthma. Other risk factors for asthma include increased viral infections during early childhood, exposure to tobacco smoke and air pollution (3). Non-allergic or non-atopic asthma is a less common type of asthma, which is frequently characterized by the infiltration and activation of neutrophils (4). Although the exact pathophysiology is not clear, the neutrophilic inflammation may be triggered by the release of cytokines from Th1 and Th17 cells or type-3 innate lymphoid cells (ILC3) upon exposure to non-allergic chemicals, including cigarette smoke and air pollutants, or microbes (5). Other endotypes of asthma include nonallergic eosinophilic asthma, which may be driven by type-2 innate lymphocytes (ILC2), and paucigranulocytic asthma, without apparent neutrophilia and eosinophilia (2).