Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
View / Open Files
Authors
Kotagiri, Prasanti
Al-Lamki, Rafia
Mescia, Federica
Bergamaschi, Laura
Turner, Lorinda
Morgan, Michael D
Calero-Nieto, Fernando J
Bach, Karsten
Wilson, Nicola K
Watts, Emily R
Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
Chinnery, Patrick F
Papadia, Sofia
Walker, Neil
Allinson, Kieren
Walmsley, Sarah R
Ouwehand, Willem H
Kasanicki, Mary
Pober, Jordan S
Publication Date
2022-03-18Journal Title
iScience
ISSN
2589-0042
Publisher
Elsevier BV
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Wang, J., Kotagiri, P., Lyons, P., Al-Lamki, R., Mescia, F., Bergamaschi, L., Turner, L., et al. (2022). Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.. iScience https://doi.org/10.1016/j.isci.2022.103971
Abstract
Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.
Sponsorship
National Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
Identifiers
External DOI: https://doi.org/10.1016/j.isci.2022.103971
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334465
Rights
Attribution 4.0 International (CC BY)
Licence URL: http://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk