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dc.contributor.authorWang, Jun
dc.contributor.authorKotagiri, Prasanti
dc.contributor.authorLyons, Paul
dc.contributor.authorAl-Lamki, Rafia
dc.contributor.authorMescia, Federica
dc.contributor.authorBergamaschi, Laura
dc.contributor.authorTurner, Lorinda
dc.contributor.authorMorgan, Michael D
dc.contributor.authorCalero-Nieto, Fernando J
dc.contributor.authorBach, Karsten
dc.contributor.authorMende, Nicole
dc.contributor.authorWilson, Nicola K
dc.contributor.authorWatts, Emily R
dc.contributor.authorCambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
dc.contributor.authorMaxwell, Patrick
dc.contributor.authorChinnery, Patrick F
dc.contributor.authorKingston, Nathalie
dc.contributor.authorPapadia, Sofia
dc.contributor.authorStirrups, Kathleen
dc.contributor.authorWalker, Neil
dc.contributor.authorGupta, Ravindra
dc.contributor.authorMenon, David
dc.contributor.authorAllinson, Kieren
dc.contributor.authorAitken, Sarah
dc.contributor.authorToshner, Mark
dc.contributor.authorWeekes, Michael
dc.contributor.authorNathan, James
dc.contributor.authorWalmsley, Sarah R
dc.contributor.authorOuwehand, Willem H
dc.contributor.authorKasanicki, Mary
dc.contributor.authorGottgens, Berthold
dc.contributor.authorMarioni, John
dc.contributor.authorSmith, Kenneth
dc.contributor.authorPober, Jordan S
dc.contributor.authorBradley, John
dc.date.accessioned2022-02-26T00:30:32Z
dc.date.available2022-02-26T00:30:32Z
dc.date.issued2022-03-18
dc.identifier.issn2589-0042
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334465
dc.description.abstractClotting 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.
dc.publisherElsevier BV
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleCoagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
dc.typeArticle
dc.publisher.departmentoffice of The School of Clinical Medicine
dc.date.updated2022-02-25T10:52:53Z
prism.publicationNameiScience
dc.identifier.doi10.17863/CAM.81882
dcterms.dateAccepted2022-02-17
rioxxterms.versionofrecord10.1016/j.isci.2022.103971
rioxxterms.versionAM
dc.contributor.orcidWang, Jun [0000-0003-3667-3760]
dc.contributor.orcidLyons, Paul [0000-0001-7035-8997]
dc.contributor.orcidMende, Nicole [0000-0002-5078-2333]
dc.contributor.orcidMaxwell, Patrick [0000-0002-0338-2679]
dc.contributor.orcidKingston, Nathalie [0000-0002-9190-2231]
dc.contributor.orcidStirrups, Kathleen [0000-0002-6823-3252]
dc.contributor.orcidGupta, Ravindra [0000-0001-9751-1808]
dc.contributor.orcidMenon, David [0000-0002-3228-9692]
dc.contributor.orcidAitken, Sarah [0000-0002-1897-4140]
dc.contributor.orcidToshner, Mark [0000-0002-3969-6143]
dc.contributor.orcidWeekes, Michael [0000-0003-3196-5545]
dc.contributor.orcidNathan, James [0000-0002-0248-1632]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidMarioni, John [0000-0001-9092-0852]
dc.contributor.orcidSmith, Kenneth [0000-0003-3829-4326]
dc.contributor.orcidBradley, John [0000-0002-7774-8805]
dc.identifier.eissn2589-0042
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
cam.orpheus.successWed Mar 23 10:26:37 GMT 2022 - Embargo updated*
cam.depositDate2022-02-25
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-03-18


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