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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression. Research (Wash D C) 2023;6:0236

Date

10/09/2023

Pubmed ID

37808178

Pubmed Central ID

PMC10551749

DOI

10.34133/research.0236

Scopus ID

2-s2.0-85175466200 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein IbĪ± and hepatic Ashwell-Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

Author List

Li J, Karakas D, Xue F, Chen Y, Zhu G, Yucel YH, MacParland SA, Zhang H, Semple JW, Freedman J, Shi Q, Ni H

Author

Qizhen Shi MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin