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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

Li, June ; Karakas, Danielle ; Xue, Feng ; Chen, Yingyu ; Zhu, Guangheng ; Yucel, Yeni H. ; MacParland, Sonya A. ; Zhang, Haibo ; Semple, John W. LU and Freedman, John , et al. (2023) In Research 6.
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 Ibα and hepatic Ashwell-Morell receptor.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Research
volume
6
article number
0236
publisher
Science Partner Journals
external identifiers
  • pmid:37808178
  • scopus:85175466200
ISSN
2096-5168
DOI
10.34133/research.0236
language
English
LU publication?
yes
id
495e293b-fa3b-4303-90ba-b4fe33fa4ee1
date added to LUP
2023-12-06 12:29:51
date last changed
2024-04-19 07:02:58
@article{495e293b-fa3b-4303-90ba-b4fe33fa4ee1,
  abstract     = {{<p>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.</p>}},
  author       = {{Li, June and Karakas, Danielle and Xue, Feng and Chen, Yingyu and Zhu, Guangheng and Yucel, Yeni H. and MacParland, Sonya A. and Zhang, Haibo and Semple, John W. and Freedman, John and Shi, Qizhen and Ni, Heyu}},
  issn         = {{2096-5168}},
  language     = {{eng}},
  publisher    = {{Science Partner Journals}},
  series       = {{Research}},
  title        = {{Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression}},
  url          = {{http://dx.doi.org/10.34133/research.0236}},
  doi          = {{10.34133/research.0236}},
  volume       = {{6}},
  year         = {{2023}},
}