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A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis

McLaughlin, Katie-May, Bojkova, Denisa, Kandler, Joshua D., Bechtel, Marco, Reus, Philipp, Le, Trang, Rothweiler, Florian, Wagner, Julian U. G., Weigert, Andreas, Ciesek, Sandra, and others. (2021) A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Current Issues in Molecular Biology, 43 (3). pp. 1212-1225. ISSN 1467-3037. E-ISSN 1467-3045. (doi:10.3390/cimb43030086) (KAR id:91273)

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Official URL:
https://doi.org/10.3390/cimb43030086

Abstract

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.

Item Type: Article
DOI/Identification number: 10.3390/cimb43030086
Uncontrolled keywords: SARS-CoV-2; COVID-19; antiviral therapy; coronavirus; IAP; CD47; SIRPalpha
Subjects: Q Science > QR Microbiology > QR355 Virology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 02 Nov 2021 16:02 UTC
Last Modified: 14 Nov 2022 23:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91273 (The current URI for this page, for reference purposes)
Wass, Mark N.: https://orcid.org/0000-0001-5428-6479
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
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