Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors.


Journal

Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028

Informations de publication

Date de publication:
11 2020
Historique:
received: 13 05 2020
revised: 20 05 2020
accepted: 25 05 2020
pubmed: 5 6 2020
medline: 15 12 2020
entrez: 5 6 2020
Statut: ppublish

Résumé

Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4 ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.

Sections du résumé

BACKGROUND
Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19.
METHODS
We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4
RESULTS
ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis.
CONCLUSIONS
Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.

Identifiants

pubmed: 32496587
doi: 10.1111/all.14429
pmc: PMC7300910
doi:

Substances chimiques

BSG protein, human 0
Basigin 136894-56-9
DPP4 protein, human EC 3.4.14.5
Dipeptidyl Peptidase 4 EC 3.4.14.5
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2829-2845

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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Auteurs

Urszula Radzikowska (U)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.

Mei Ding (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Ge Tan (G)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Functional Genomic Centre Zurich, ETH Zurich/University of Zurich, Zurich, Switzerland.

Damir Zhakparov (D)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Yaqi Peng (Y)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Paulina Wawrzyniak (P)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Division of Clinical Chemistry and Biochemistry, University Children`s Hospital Zurich, Zurich, Switzerland.
Children`s Research Center, University Children`s Hospital Zurich, Zurich, Switzerland.

Ming Wang (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University and the Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.

Shuo Li (S)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Hideaki Morita (H)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

Can Altunbulakli (C)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.

Matthias Reiger (M)

Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen, Augsburg, Germany.

Avidan U Neumann (AU)

Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen, Augsburg, Germany.
Institute of Computational Biology (ICB), Helmholtz Zentrum Munchen, Munich, Germany.
Institute of Experimental Medicine (IEM), Czech Academy of Sciences, Prague, Czech Republic.

Nonhlanhla Lunjani (N)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.

Claudia Traidl-Hoffmann (C)

Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.
Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum Munchen, Augsburg, Germany.

Kari C Nadeau (KC)

Sean N Parker Centre for Allergy and Asthma Research at Stanford University, Department of Medicine, Stanford University School of Medicine, Stanford, USA.

Liam O'Mahony (L)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Department of Medicine and School of Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, Ireland.

Cezmi Akdis (C)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.

Milena Sokolowska (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne - Center for Research and Education (CK-CARE), Davos, Switzerland.

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