Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells

J Allergy Clin Immunol. 2020 Jul;146(1):80-88.e8. doi: 10.1016/j.jaci.2020.05.004. Epub 2020 May 15.

Abstract

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.

Keywords: ACE2; Asthma; COVID-19; IL-13; SARS-CoV-2; TMPRSS2; airway epithelial cells; nasal epithelial cells; type 2 inflammation.

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2
  • Asthma / immunology*
  • Asthma / metabolism
  • Betacoronavirus / immunology
  • COVID-19
  • Child
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / metabolism
  • Female
  • Humans
  • Hypersensitivity, Immediate / immunology*
  • Hypersensitivity, Immediate / metabolism
  • Inflammation / immunology
  • Inflammation / virology
  • Interleukin-13 / immunology*
  • Interleukin-13 / pharmacology
  • Male
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / metabolism
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • SARS-CoV-2
  • Serine Endopeptidases / metabolism*

Substances

  • Interleukin-13
  • interleukin-13, human
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human