TY - JOUR
T1 - Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells
AU - Kimura, Hiroki
AU - Francisco, Dave
AU - Conway, Michelle
AU - Martinez, Fernando D.
AU - Vercelli, Donata
AU - Polverino, Francesca
AU - Billheimer, Dean
AU - Kraft, Monica
N1 - Publisher Copyright:
© 2020
PY - 2020/7
Y1 - 2020/7
N2 - Background: Severe acute respiratory syndrome coronavirus 2 (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 comorbid conditions associated with COVID-19. Objective: Our aim was to extend our work in IL-13 biology to determine whether airway epithelial cell expression of 2 key mediators critical for SARS-CoV-2 infection, namely, 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 2 data sets 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 2 independent data sets, ACE2 expression was significantly reduced and TMPRSS2 expression 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, whereas TMPRSS2 expression was significantly positively associated with type 2 cytokines. Conclusion: IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma and atopy. This deserves further study with regard to any effects that asthma and atopy may render in the setting of COVID-19 infection.
AB - Background: Severe acute respiratory syndrome coronavirus 2 (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 comorbid conditions associated with COVID-19. Objective: Our aim was to extend our work in IL-13 biology to determine whether airway epithelial cell expression of 2 key mediators critical for SARS-CoV-2 infection, namely, 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 2 data sets 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 2 independent data sets, ACE2 expression was significantly reduced and TMPRSS2 expression 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, whereas TMPRSS2 expression was significantly positively associated with type 2 cytokines. Conclusion: IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma and atopy. This deserves further study with regard to any effects that asthma and atopy may render in the setting of COVID-19 infection.
KW - ACE2
KW - Asthma
KW - COVID-19
KW - IL-13
KW - SARS-CoV-2
KW - TMPRSS2
KW - airway epithelial cells
KW - nasal epithelial cells
KW - type 2 inflammation
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U2 - 10.1016/j.jaci.2020.05.004
DO - 10.1016/j.jaci.2020.05.004
M3 - Article
C2 - 32422146
AN - SCOPUS:85086171260
SN - 0091-6749
VL - 146
SP - 80-88.e8
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -