Back to Search
Start Over
Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Funder: Royal Australasian College of Physicians<br />Funder: NIHR<br />Funder: UKRI<br />Funder: Chief Scientist Office<br />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.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6c5091ee2db4808bc4ceff5415059a63