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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19
iScience, Volume 25, No. 3, Article 103971, Year 2022
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Description
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. © 2022 The Authors
Authors & Co-Authors
Lyons, Paul A.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Mescia, Federica
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Bergamaschi, Laura
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Morgan, Michael D.L.
United Kingdom, Cambridge
Cancer Research uk Cambridge Institute
United Kingdom, Cambridge
University of Cambridge
Chinnery, Patrick Francis
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Kingston, Nathalie
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Papadia, Sofia
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Stirrups, Kathleen E.
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Cambridge
University of Cambridge
Gupta, Ravindra K.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Menon, David Krishna
United Kingdom, Cambridge
University of Cambridge
Toshner, Mark R.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
Royal Papworth Hospital Nhs Foundation Trust
Weekes, Michael P.
United Kingdom, Cambridge
Addenbrooke's Hospital
Nathan, James A.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Ouwehand, Willem Hendrik
United Kingdom, Cambridge
Wellcome - Mrc Cambridge Stem Cell Institute
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
United Kingdom, Bristol
Nhs Blood and Transplant
Marioni, John Carlo
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
Cancer Research uk Cambridge Institute
United Kingdom, Hinxton
Embl’s European Bioinformatics Institute
Smith, Kenneth G.C.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
University of Cambridge
Bradley, John Richard
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
Cambridge University Hospitals Nhs Foundation Trust
Statistics
Citations: 4
Authors: 17
Affiliations: 12
Identifiers
Doi:
10.1016/j.isci.2022.103971
ISSN:
25890042
Research Areas
Covid