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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.authorJohnson, 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.accessioned2022-03-31T01:02:24Z
dc.date.available2022-03-31T01:02:24Z
dc.date.issued2022-03-18
dc.identifier.issn2589-0042
dc.identifier.other35224470
dc.identifier.otherPMC8863325
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335536
dc.descriptionFunder: Royal Australasian College of Physicians
dc.descriptionFunder: NIHR
dc.descriptionFunder: UKRI
dc.descriptionFunder: Chief Scientist Office
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.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2589-0042
dc.sourcenlmid: 101724038
dc.subjectMicrobiology
dc.subjectimmunology
dc.subjectTranscriptomics
dc.subjectOmics
dc.titleCoagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
dc.typeArticle
dc.date.updated2022-03-31T01:02:21Z
prism.issueIdentifier3
prism.publicationNameiScience
prism.volume25
dc.identifier.doi10.17863/CAM.82969
dcterms.dateAccepted2022-02-17
rioxxterms.versionofrecord10.1016/j.isci.2022.103971
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
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.orcidJohnson, 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
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
pubs.funder-project-idMedical Research Council (G0900951)
pubs.funder-project-idWellcome Trust (212219/Z/18/Z)
pubs.funder-project-idMedical Research Council (MR/S036113/1)
pubs.funder-project-idWellcome Trust (215477/Z/19/Z)
pubs.funder-project-idMedical Research Council (MC_PC_17230)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International