@article{fc5028b7958a4563963eb4264170528b,
title = "Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19",
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 = "Immunology, Microbiology, Omics, Transcriptomics",
author = "Jun Wang and Prasanti Kotagiri and Lyons, {Paul A} and Al-Lamki, {Rafia S} and Federica Mescia and Laura Bergamaschi and Lorinda Turner and Morgan, {Michael D} and Calero-Nieto, {Fernando J} and Karsten Bach and Nicole Mende and Wilson, {Nicola K} and Watts, {Emily R} and Maxwell, {Patrick H} and Chinnery, {Patrick F} and Nathalie Kingston and Sofia Papadia and Stirrups, {Kathleen E} and Neil Walker and Gupta, {Ravindra K} and Menon, {David K} and Kieren Allinson and Aitken, {Sarah J} and Mark Toshner and Weekes, {Michael P} and Nathan, {James A} and Walmsley, {Sarah R} and Ouwehand, {Willem H} and Mary Kasanicki and Berthold G{\"o}ttgens and Marioni, {John C} and Smith, {Kenneth G C} and Pober, {Jordan S} and Bradley, {John R} and {Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration}",
note = "This work was supported by the NIHR BioResource, the NIHR Cambridge Biomedical Research Centre and the NIHR Cambridge Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. FV plasma assays were performed by the NIHR Cambridge Biochemical Assay Laboratory. The Cambridge University Hospitals Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. FV constructs were prepared and expressed by Peak Proteins. Neutrophil proteins were characterized at the Mass Spectrometry Facility at the University of Dundee and the QMRI flow cytometry and cell sorting facility. Sequencing was supported by Paul Coupland from the CRUK Cambridge Institute Genomics Core. The graphical abstract was produced using Biorender (https://biorender.com/). The work was funded by awards from NIHR to the NIHR BioResource and the NIHR Cambridge Biomedical Research Centre, Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR funding through the UK Coronavirus Immunology Consortium (UK-CIC) and a CSO award (COV/DUN/20/01). KGCS holds a Wellcome Trust Investigator award. BG holds an award from the Aging Biology Foundation Europe to BG. RKG holds a Wellcome Senior Fellowship (WT108082AIA). PK is supported by the Australian and New Zealand Society of Nephrology and the Royal Australasian College of Physicians. SRW holds a Wellcome Trust Senior Clinical Fellowship (209220). ERW holds a Wellcome Clinical Training Fellowship award (108717/Z/15/Z). NM was supported by a DFG Research Fellowship. PFC is a Wellcome Trust Principal Research Fellow (212219/Z/18/Z), and a NIHR Senior Investigator, and receives support from the Medical Research Council (MRC) Mitochondrial Biology Unit, the MRC International Centre for Genomic Medicine in Neuromuscular Disease, the Leverhulme Trust, an MRC research grant, and an Alzheimer's Society Project Grant. JAN holds a Wellcome Trust Senior Research Fellowship (215477/Z/19/Z).",
year = "2022",
month = mar,
day = "18",
doi = "10.1016/j.isci.2022.103971",
language = "English",
volume = "25",
pages = "103971",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "3",
}