Figure 1. Schematic representation of the functional crosstalk between AECs and innate and adaptive immune cells. Airway inflammation is initiated by epithelial cells. AECs express many PRRs to rapidly detect and respond to internal or external environmental agents including pollutants, viruses and allergens causing the release of remodeling factors and bronchoconstrictor agents as well as pro-inflammatory chemokines and cytokines. These latter mediators enable AECs to bridge the gap between the innate and adaptive immune systems.
Alarmins (TSLP, IL-25 and IL-33) activate ILC2s, which are potent producers of IL-5 and IL-13, participating in type 2 airway inflammation. The interaction between TSLP and antigen presenting cells such as DCs that present inhaled antigens to T and B cells resulting in Th2 differentiation and IgE production plays an important role in the sensitization of inhaled allergens. The maturation of dendritic cells promotes the generation of effector T cells and triggers the release of direct bronchial contractors and Th2 cytokines, which feed back on the epithelium and airway smooth muscle and further facilitate amplification of airway inflammation through subsequent adaptive T cell responses. AECs also release periostin, which further boosts TGF (transforming growth factor)-β production, activating the underlying fibroblasts to differentiate into myofibroblasts, participating in the formation of airway remodeling.