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Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19
- Source :
- iScience, Vol 25, Iss 3, Pp 103971- (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
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.
- Subjects :
- Immunology
Microbiology
Omics
Transcriptomics
Science
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 25
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.6a5d77411f514ca9917df8b819d1dc92
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2022.103971