IL-13Rα2/AP-1 complex signalling mediates airway epithelial repair without effects on remodeling pathways

Objective/purpose The airway epithelium serves as a physical defense barrier to the external environment for the underlying tissue and suffers frequent injury. The response to injury is inflammation followed by debris clearance and repair. Although IL-13 is known to be a key cytokine in mediating inflammatory and remodeling responses via signal transducer and activator of transcription 6 (STAT6) and early growth response protein 1 (Egr1), our laboratory has demonstrated that IL-13 is critical to airway epithelial repair via the release of heparin-binding epidermal growth factor (HB-EGF) and activation of epidermal growth factor receptor (EGFR). IL-13 signals through two receptors, IL-13Ra1/IL-4R and IL-13Ra2. IL-13Ra2 has previously been thought to act exclusively as a decoy receptor, however our findings show that IL13Ra2 can act as a signaling receptor and is involved in mediating airway epithelial repair. Differential signaling via IL-13Ra1 or IL-13Ra2 may determine a remodeling versus repair response to injury in airway epithelium.