Distinct expression of SARS‐CoV‐2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps

• Published in: Allergy 2021-03, Vol.76 (3), p.789-803
• Main Authors: Wang, Ming, Bu, Xiangting, Fang, Gaoli, Luan, Ge, Huang, Yanran, Akdis, Cezmi A., Wang, Chengshuo, Zhang, Luo
• Format: Article
• Language: English
• Subjects: ACE2; Adult; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - genetics; Cells, Cultured; Chronic Disease; chronic rhinosinusitis with nasal polyps; Coronaviruses; COVID-19 - etiology; Epithelial cells; Female; Gene Expression Regulation, Enzymologic; Glucocorticoids; Glucocorticoids - pharmacology; Humans; Inflammation; inflammatory endotype; Interferon; Interleukin 1; Interleukin 13; Interleukin 5; Leukocytes (eosinophilic); Male; Middle Aged; Nasal Polyps - enzymology; Nasal Polyps - immunology; Original; ORIGINAL ARTICLES; Polyps; Receptors, Coronavirus - genetics; Rhinitis; Rhinitis - enzymology; Rhinitis - immunology; Rhinosinusitis; SARS‐CoV‐2; Serine Endopeptidases - genetics; Severe acute respiratory syndrome coronavirus 2; Sinusitis; Sinusitis - enzymology; Sinusitis - immunology; TMPRSS2
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.14665

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. Methods The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. Results ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. Conclusion These findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation. The expression of SARS‐CoV‐2 receptor ACE2 is significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects. ACE2 expression is increased in nasal tissues of type 1 endotype of CRSwNP and positively correlated with the expression of IFN‐γ. IFN‐γ up‐regulates ACE2 expression while glucocorticoids attenuate this increase in cultured nasal epithelial cells. Abbreviations: ACE2, angiotensin‐converting enzyme 2; ECRSwNP, eosinophilic chronic rhinosinusitis with nasal polyps; non‐ECRSwNP, noneosinophilic chronic rhinosinusitis with nasal polyps; SARS‐CoV‐2, severe acute respiratory syndrome