IL-13 Signaling through IL-13 Receptor α2 Mediates Airway Epithelial Wound Repair
This week we profile a recent publication in the FASEB Journal from the laboratory of
Dr. Delbert Dorscheid at the Centre for Heart Lung Innovation at St. Paul’s Hospital.
Can you provide a brief overview of your lab’s current research focus?
My lab research program focuses on the airway epithelium and its role in the regulation of lung inflammation. The inappropriate inflammation of the airway wall contributes to conditions such as asthma and COPD. Our focus is to understand the normal functioning of the airway epithelium as a barrier. The barrier is not just to function as a physical protector of the lung against noxious and injurious particles but also as an immune organ. The airway epithelium, when in contact with inhaled particles, can respond in a variety of steps. The epithelial goblet cells and airway glands produce and secrete mucous. This mucous can trap and bind particles and facilitate their removal by the mechanism of mucociliary clearance. The airway epithelial cells may also initiate an inflammatory response. The epithelium can generate lipid mediators, IL6 and 8 and a variety of immune cell chemo-attractants. The epithelium also expresses immune globulin receptors and can present antigen to airway wall dendritic cells – thus contributing to a more specific immune response. An “intact” airway epithelium is “anti-inflammatory” for the airway while a “damaged” epithelium generates “inflammation”. If an airway epithelium is chronically injured or damaged, this may contribute to the generation of asthma and COPD. The role of IL13 is to promote repair of the airway epithelium and re-establish homeostasis of the airway wall – this process is defective in asthma.
What is the significance of the findings in this publication?
The results presented in this manuscript demonstrate the role for the IL13 receptor Rα2 in mediating repair of injured airway epithelium. We also demonstrated that the expression of IL13Rα2 is dramatically and significantly reduced in the airway epithelium of asthmatic individuals. This provides insight into the historical findings of epithelial damage and inflammation, in particular elevated IL13, in asthma. It may not be appropriate to block or absorb IL13 in asthma therapies, instead facilitating repair of the airway epithelium via IL13 becomes a new target for novel therapeutics.
What are the next steps for this research?
It was previously believed that IL13Rα2 was non-signalling and functioned as a decoy receptor. We continue to investigate other receptor subunits and heterodimer formation with IL13Rα2 to fully understand how this receptor signals to coordinate repair of the airway epithelium. We are also studying small molecule ligands for IL13Rα2 as a therapeutic intervention.
This work was funded by:
Funded by Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, Allergen NCE, BC Lung Association, and Providence Health Care Department of Medicine.