Details

Autor(en) / Beteiligte

• Wang, Jun
• Kotagiri, Prasanti
• Lyons, Paul A.
• Al-Lamki, Rafia S.
• Mescia, Federica
• Bergamaschi, Laura
• Turner, Lorinda
• Morgan, Michael D.
• Calero-Nieto, Fernando J.
• Bach, Karsten
• Mende, Nicole
• Wilson, Nicola K.
• Watts, Emily R.
• Maxwell, Patrick H.
• Chinnery, Patrick F.
• Kingston, Nathalie
• Papadia, Sofia
• Stirrups, Kathleen E.
• Walker, Neil
• Gupta, Ravindra K.
• Menon, David K.
• Allinson, Kieren
• Aitken, Sarah J.
• Toshner, Mark
• Weekes, Michael P.
• Nathan, James A.
• Walmsley, Sarah R.
• Ouwehand, Willem H.
• Kasanicki, Mary
• Göttgens, Berthold
• Marioni, John C.
• Smith, Kenneth G.C.
• Pober, Jordan S.
• Bradley, John R.

Titel

Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19

Ist Teil von

• iScience, 2022-03, Vol.25 (3), p.103971, Article 103971

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• 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. [Display omitted] •Neutrophils, T-cells including T regulatory cells, and monocytes produce Factor V•Leukocyte expression of Factor V increases in COVID-19•Factor V suppresses T conventional cell proliferation in vitro•Leukocyte Factor V expression correlated with lymphopenia in COVID-19 Immunology; Microbiology; Omics; Transcriptomics