Epithelial-mesenchymal interactions in the pathogenesis of asthma

Abstract

Asthma is regarded as an inflammatory disorder of the conducting airways characterized by a mast cell, eosin­ophil and T lymphocyte inflammatory response that is responsive to anti‐inflammatory therapy, such as corticosteroids. In more severe and chronic disease, corticosteroids become less effective. As in other chronic inflammatory diseases, the tissue in which the cellular and mediator processes occur plays a major role in maintaining the response and creating a basis for disease persistence. Herein, we describe evidence that the airway epithelium interacting with the underlying mesenchymal cells recapitulates branching morphogenesis, as observed in the developing lung, to create airway wall remodeling. The reciprocal signaling between the susceptible epithelium and responsive mesenchyme (epithelial mesenchymal trophic unit) offers a new paradigm for asthma and creates new opportunities for developing therapeutics based on reversing the ‘chronic wound’ phenotype of asthmatic airways.

Session 1: Allergic disease Nutrition as a potential determinant of asthma

“…inflammation plays a central role in asthma, it appears that the airway epithelium contributes to the airway inflammatory response (7,8) . The airway epithelium of individuals with asthma appears to be intrinsically abnormal, with increased susceptibility to injury and impaired ability to repair resulting in a chronic pro-inflammatory milieu and airway remodelling (7,8) .…”

“…The airway epithelium of individuals with asthma appears to be intrinsically abnormal, with increased susceptibility to injury and impaired ability to repair resulting in a chronic pro-inflammatory milieu and airway remodelling (7,8) .…”

“…Airway development occurs predominantly antenatally and is nearly complete by birth; subsequent development is limited to increases in length and diameter (82) . Disturbances of respiratory epithelial and mesenchymal development, particularly branching morphogenesis, have been implicated in the pathogenesis of asthma (7,8) and it is possible that suboptimal fetal nutrient status adversely affects respiratory epithelial and mesenchymal development resulting in suboptimal earlylife airway function. Such an adverse effect on fetal airway development will be associated with an increased risk of developing asthma because reduced neonatal lung function is associated with an increased risk of wheezing and asthma in later childhood (74,83) .…”

Bleomycin‐induced lung injury assessed noninvasively and in spontaneously breathing rats by proton MRI

“…In patients with chronic obstructive pulmonary disease (COPD) a patchy alveolar wall fibrosis develops whereas in chronic asthmatics, a fibrotic response occurs predominantly in the lamina reticularis, leading to a thickening of the basement membrane (4,5). In both cases the ongoing inflammation-repair cycle leads to permanent structural changes in the airway wall (remodeling) of which fibrosis is a major constituent (6,7). However, up to 50% of the cases of pulmonary fibrosis are defined as idiopathic pulmonary fibrosis (8).…”

Le remodelage bronchique dans l’asthme : mécanismes et enjeux thérapeutiques

“…Dans l'asthme sévère, une perte des cellules basales peut égale-ment être observée [4,11]. Ces observations ont fait évo-quer des anomalies de la réparation épithéliale à l'origine du remodelage des voies aériennes dans l'asthme [17,18]. En effet, ces anomalies pourraient perpétuer le contact entre les allergènes et les structures sous-épithéliales et favoriser ainsi le maintien de l'inflammation tissulaire.…”