{"doi":"10.34133/research.0236","title":"Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression","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. 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.","journal":"Research","year":2023,"id":324395,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1040464,"name":"Danielle Karakas","orcid":"0009-0002-5218-756X","position":1,"is_corresponding":false},{"id":1040465,"name":"Feng Xue","orcid":"0000-0002-5947-3924","position":2,"is_corresponding":false},{"id":879909,"name":"Yingyu Chen","orcid":"0000-0003-1243-3607","position":3,"is_corresponding":false},{"id":1041059,"name":"Guangheng Zhu","orcid":null,"position":4,"is_corresponding":false},{"id":1041060,"name":"Yeni H. Yücel","orcid":null,"position":5,"is_corresponding":false},{"id":34167,"name":"Sonya A. MacParland","orcid":"0000-0002-8036-1425","position":6,"is_corresponding":false},{"id":1040466,"name":"Haibo Zhang","orcid":"0000-0002-1714-3038","position":7,"is_corresponding":false},{"id":308482,"name":"John W. Semple","orcid":"0000-0002-1510-0077","position":8,"is_corresponding":false},{"id":1041061,"name":"John Freedman","orcid":null,"position":9,"is_corresponding":false},{"id":454533,"name":"Qizhen Shi","orcid":"0000-0003-1548-0708","position":10,"is_corresponding":false},{"id":968639,"name":"Heyu Ni","orcid":"0000-0002-7621-2945","position":11,"is_corresponding":false},{"id":723184,"name":"June Li","orcid":"0009-0007-6242-5839","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-19T01:08:11.275604Z","pmid":"37808178","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}