Involvement of the Epidermal Growth Factor Receptor in IL-13 Mediated, Corticosteroid-Resistant Airway Inflammation

Jan 17, 2020

Severe, difficult-to-treat asthma is poorly controlled by current medications and often does not respond at all to the mainstay drugs, called corticosteroids. Consequently, severe asthma impairs quality of life and is a substantial burden on healthcare resources. To understand mechanisms underlying difficult asthma, we have studied a mouse model in which a pro-allergic chemical signal called ‘Interleukin-13’ (IL-13) was used to cause asthma-like symptoms in the lungs of the mice. We used this as a model for severe, difficult-to-treat asthma in which the mainstay drugs, called corticosteroids can only reduce allergic responses and not airway twitchiness or the non-allergic responses. Therefore, we wanted to see if we could target these resistant responses in another way. We had previously identified a signalling molecule, called ‘Epithelial Growth Factor Receptor’ (EGFR), as the driver of the non-allergic response, so put a drug that blocks EGFR into the model alongside the corticosteroids.

When given alone, we can show that blocking EGFR successfully reduced airway twitchiness and the non-allergic reactions occurring in the airway, but it was unable to limit the allergic responses. However, when given alongside the corticosteroids, we could block both the allergic and non-allergic reactions as well as the airway twitchiness.

In addition to this, we were able to compare these findings to existing patient data, and identify different groups of patients based on their clinical characteristics. One group of patients in particular were shown to have expression of IL-13 in the cells that line the inner surface of the airways, suggesting that our mouse model, which expresses IL-13 in the same way, mirrors a sub-cluster of the human disease.

The award from the AAIR Charity enabled Dr Davies to conduct these experiments to finish off a body of work that was a part of her PhD studies. The results have been presented at national and international meetings and have just been published in Clinical & Experimental Allergy.

We thank the AAIR Charity for their contribution to our research.