Dynamic role of epithelium-derived cytokines in asthma

Asthma is an inflammatory disorder of the airways, characterized by infiltration of mast cells, eosinophils, and Th2-type CD4+ T cells in the airway wall. Airway epithelium constitutes the first line of interaction with our atmospheric environment. The protective barrier function of the airway epithelium is likely impaired in asthma. Furthermore, recent studies suggest critical immunogenic and immunomodulatory functions of airway epithelium. In particular, a triad of cytokines, including IL-25, IL-33 and TSLP, is produced and released by airway epithelial cells in response to various environmental and microbial stimuli or by cellular damage. These cytokines induce and promote Th2-type airway inflammation and cause remodeling and pathological changes in the airway walls, suggesting their pivotal roles in the pathophysiology of asthma. Thus, the airway epithelium can no longer be regarded as a mere structural barrier, but must be considered an active player in the pathogenesis of asthma and other allergic disorders.

► Airway epithelium plays barrier and immune regulatory roles in asthma.
► Epithelium-derived cytokines, IL-25, IL-33 and TSLP, promote type 2 immune responses.
► They may create a positive feedback loop promoting airway inflammation and remodeling.
► Therapy targeting these cytokines may be effective to prevent or attenuate asthma.