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Desialylated Platel...
Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression
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- Li, June (author)
- Li Ka Shing Knowledge Institute,University of Toronto,Canadian Blood Services
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- Karakas, Danielle (author)
- Li Ka Shing Knowledge Institute,University of Toronto
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- Xue, Feng (author)
- BloodCenter of Wisconsin,Medical College of Wisconsin
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- Chen, Yingyu (author)
- BloodCenter of Wisconsin,Medical College of Wisconsin
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- Zhu, Guangheng (author)
- Li Ka Shing Knowledge Institute
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- Yucel, Yeni H. (author)
- Li Ka Shing Knowledge Institute,Ryerson University,University of Toronto
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- MacParland, Sonya A. (author)
- University of Toronto
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- Zhang, Haibo (author)
- Li Ka Shing Knowledge Institute,University of Toronto
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- Semple, John W. (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Trombocyt immunologi,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Platelet Immunology,Lund University Research Groups,Region Skåne,University of Toronto
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- Freedman, John (author)
- Li Ka Shing Knowledge Institute,University of Toronto
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- Shi, Qizhen (author)
- BloodCenter of Wisconsin,Medical College of Wisconsin
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- Ni, Heyu (author)
- Li Ka Shing Knowledge Institute,Canadian Blood Services,University of Toronto
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Research. - 2096-5168. ; 6
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Abstract
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- 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 Ibα 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Li, June
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Karakas, Daniell ...
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Xue, Feng
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Chen, Yingyu
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Zhu, Guangheng
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Yucel, Yeni H.
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show more...
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MacParland, Sony ...
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Zhang, Haibo
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Semple, John W.
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Freedman, John
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Shi, Qizhen
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Ni, Heyu
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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Research
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Lund University