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Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19 #MMPMID35224470
Wang J; Kotagiri P; Lyons PA; Al-Lamki RS; Mescia F; Bergamaschi L; Turner L; Morgan MD; Calero-Nieto FJ; Bach K; Mende N; Wilson NK; Watts ER; Maxwell PH; Chinnery PF; Kingston N; Papadia S; Stirrups KE; Walker N; Gupta RK; Menon DK; Allinson K; Aitken SJ; Toshner M; Weekes MP; Nathan JA; Walmsley SR; Ouwehand WH; Kasanicki M; Gottgens B; Marioni JC; Smith KGC; Pober JS; Bradley JR
iScience 2022[Mar]; 25 (3): 103971 PMID35224470show ga
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.