Type 2 Inflammation Modulates ACE2 and TMPRSS2 in Airway Epithelial Cells

Kimura, Hiroki; Francisco, Dave; Conway, Michelle; Martinez, Fernando D.; Vercelli, Donata; Polverino, Francesca; Billheimer, Dean; Kraft, Monica

Abstract Background SARS-CoV-2 has dramatically changed our world, country, communities and families. There is controversy regarding risk factors for severe COVID-19 disease. It has been suggested that asthma and allergy are not highly represented as co-morbid conditions associated with COVID-19. Objective To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. Methods We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. We also examined expression of ACE2 and TMPRSS2 in two datasets containing gene expression data from nasal and airway epithelial cells from children and adults with asthma and allergic rhinitis. Results IL-13 significantly reduced ACE2 and increased TMPRSS2 expression ex vivo in airway epithelial cells. In two independent datasets, ACE2 expression was significantly reduced and TMPRSS2 was significantly increased in the nasal and airway epithelial cells in type 2 asthma and allergic rhinitis. ACE2 expression was significantly negatively associated with type 2 cytokines while TMPRSS2 expression was significantly positively associated with type 2 cytokines. Conclusion IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma. This deserves further study with regard to any effects asthma and atopy may render in the setting of COVID-19 infection.