Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
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Authors
Kotagiri, Prasanti
Lyons, Paul A
Al-Lamki, Rafia S
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
Maxwell, Patrick H
Chinnery, Patrick F
Papadia, Sofia
Stirrups, Kathleen E
Walker, Neil
Gupta, Ravindra K
Menon, David K
Allinson, Kieren
Aitken, Sarah J
Weekes, Michael P
Nathan, James A
Walmsley, Sarah R
Ouwehand, Willem H
Kasanicki, Mary
Göttgens, Berthold
Marioni, John C
Smith, Kenneth GC
Pober, Jordan S
Bradley, John R
Publication Date
2022-03-18Journal Title
iScience
ISSN
2589-0042
Publisher
Elsevier BV
Volume
25
Issue
3
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Wang, J., Kotagiri, P., Lyons, P. A., Al-Lamki, R. S., Mescia, F., Bergamaschi, L., Turner, L., et al. (2022). Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.. iScience, 25 (3) https://doi.org/10.1016/j.isci.2022.103971
Description
Funder: Royal Australasian College of Physicians
Funder: NIHR
Funder: UKRI
Funder: Chief Scientist Office
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.
Keywords
Microbiology, immunology, Transcriptomics, Omics
Sponsorship
National Institute for Health Research (IS-BRC-1215-20014)
Medical Research Council (G0900951)
Wellcome Trust (212219/Z/18/Z)
Medical Research Council (MR/S036113/1)
Wellcome Trust (215477/Z/19/Z)
Medical Research Council (MC_PC_17230)
Identifiers
35224470, PMC8863325
External DOI: https://doi.org/10.1016/j.isci.2022.103971
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335536
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