학술논문
Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19
Document Type
article
Author
Jun Wang; Prasanti Kotagiri; Paul A. Lyons; Rafia S. Al-Lamki; Federica Mescia; Laura Bergamaschi; Lorinda Turner; Michael D. Morgan; Fernando J. Calero-Nieto; Karsten Bach; Nicole Mende; Nicola K. Wilson; Emily R. Watts; Patrick H. Maxwell; Patrick F. Chinnery; Nathalie Kingston; Sofia Papadia; Kathleen E. Stirrups; Neil Walker; Ravindra K. Gupta; David K. Menon; Kieren Allinson; Sarah J. Aitken; Mark Toshner; Michael P. Weekes; James A. Nathan; Sarah R. Walmsley; Willem H. Ouwehand; Mary Kasanicki; Berthold Göttgens; John C. Marioni; Kenneth G.C. Smith; Jordan S. Pober; John R. Bradley
Source
iScience, Vol 25, Iss 3, Pp 103971- (2022)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: 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.