ArticleThe Journal of clinical investigation2022
IFITM3 regulates fibrinogen endocytosis and platelet reactivity in nonviral sepsis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- IFITM3 Is Elevated in BAL and Plasma Following Infection in ICU Setting.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- From Recanalization to Failed Recovery: No Reflow, No Rescue, and No Regrow After Thrombectomy.Translational stroke research · 2026Review
- A multi-omics approach investigating thrombolysis resistance in acute ischemic stroke thrombi.Journal of thrombosis and thrombolysis · 2026Article
- Enhancing validation of case-control omics signatures through "minimalist" single-subject analysis (N-of-1 trials): proof of concept in sepsis.Journal of the American Medical Informatics Association : JAMIA · 2026Article
- MYCT1-IFITM2/3 interaction links endothelial endolysosomal trafficking to white adipose tissue expansion.The Journal of experimental medicine · 2026Article
- Development and Validation of a Nomogram for Predicting Sepsis Risk in Patients with Non-Ventilator Hospital-Acquired Pneumonia.Biomedicines · 2026Article
- Differential regulation of cyclic adenosine monophosphate by phosphodiesterase 3A discriminates thrombin-induced protease activated receptor 1- and 4-dependent platelet activation.Journal of thrombosis and haemostasis : JTH · 2026Article
- A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.Nature communications · 2026Article
- Fibrinogen exacerbates α-synuclein aggregation and mitochondrial dysfunction via alpha5beta3 integrin in Parkinson's disease.Journal of advanced research · 2026Article
- Stratified assessment of platelets in sepsis: from dynamic counts to functional phenotypes.Frontiers in immunology · 2026Review
- Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants.Journal of innate immunity · 2026Article
- Article
- Beyond Thrombopoiesis: The Immune Functions of Megakaryocytes in Bacterial Infections and Sepsis.International journal of molecular sciences · 2025Review
- Mechanisms of Differential Signal Transduction by IFNLR1 Variants.bioRxiv : the preprint server for biology · 2025Article
- Association between the changing trends of platelet distribution width and in-hospital mortality in critically ill patients with sepsis: a multicenter study based on machine learning.BMC infectious diseases · 2025Article
- Neutrophil degranulation is increased at seven days after human intracerebral hemorrhage, but not at 72 h, and correlates with decreased miR-3613 and miR-3690.BMC neurology · 2025Article
- The predictive value of platelet parameters and hemorheological indicators for elderly sepsis patients.BMC anesthesiology · 2025Article
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- Single-cell transcriptomic and m6A methylation analyses reveal platelet-mediated immune regulatory mechanisms in sepsis.Frontiers in immunology · 2025Article
- Immunological face of megakaryocytes.Frontiers of medicine · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection and inflammation alter the megakaryocyte and platelet transcriptome to induce altered platelet reactivity. We determined whether nonviral sepsis induces differential platelet gene expression and reactivity. Nonviral sepsis upregulated IFN-induced transmembrane protein 3 (IFITM3), an IFN-responsive gene that restricts viral replication. As IFITM3 has been linked to clathrin-mediated endocytosis, we determined whether IFITM3 promoted endocytosis of α-granule proteins. IFN stimulation enhanced fibrinogen endocytosis in megakaryocytes and platelets from Ifitm+/+ mice, but not Ifitm-/- mice. IFITM3 overexpression or deletion in megakaryocytes demonstrated IFITM3 was necessary and sufficient to regulate fibrinogen endocytosis. Mechanistically, IFITM3 interacted with clathrin and αIIb and altered their plasma membrane localization into lipid rafts. In vivo IFN administration increased fibrinogen endocytosis, platelet reactivity, and thrombosis in an IFITM-dependent manner. In contrast, Ifitm-/- mice were completely rescued from IFN-induced platelet hyperreactivity and thrombosis. During murine sepsis, platelets from Ifitm+/+ mice demonstrated increased fibrinogen content and platelet reactivity, which was dependent on IFN-α and IFITMs. Platelets from patients with nonviral sepsis had increases in platelet IFITM3 expression, fibrinogen content, and hyperreactivity. These data identify IFITM3 as a regulator of platelet endocytosis, hyperreactivity, and thrombosis during inflammatory stress.
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Registered trials
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