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.