ArticleImmunity2022
Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.Military Medical Research · 2023Trial
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- STING-Dependent spontaneous platelet adhesion potentiates NK cell proinflammatory responses in pediatric crohn's disease.Blood research · 2025Article
- The predictive value of platelet parameters and hemorheological indicators for elderly sepsis patients.BMC anesthesiology · 2025Article
- Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.Acta pharmaceutica Sinica. B · 2025Article
- Association between platelet to lymphocyte ratio and febrile urinary tract infection after double-J stent removal in children underwent laparoscopic pyeloplasty.BMC urology · 2025Article
- Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?ChemMedChem · 2025Review
- Platelets and Their Role in Immunity: Formation, Activation and Activity, and Biologically Active Substances in Their Granules and Extracellular Vesicles.International journal of inflammation · 2025Review
- Characterization of Platelet Receptors and Their Involvement in Immune Activation of These Cells.International journal of molecular sciences · 2024Review
- Pyroptotic Macrophage-Derived Microvesicles Accelerate Formation of Neutrophil Extracellular TrapsInternational journal of biological sciences · 2024Article
- Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology.Nature immunology · 2023Article
- Neutrophil intrinsic and extrinsic regulation of NETosis in health and disease.Trends in microbiology · 2023Review
- Platelet, a key regulator of innate and adaptive immunity.Frontiers in medicine · 2023Review
- Platelet-monocyte aggregates: molecular mediators of thromboinflammation.Frontiers in cardiovascular medicine · 2023Review
- Article
- NFAT: platelet stickiness regulator.Nature reviews. Immunology · 2022Article
- The role of extracellular traps in ischemia reperfusion injury.Frontiers in immunology · 2022Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
During gram-negative septicemia, interactions between platelets and neutrophils initiate a detrimental feedback loop that sustains neutrophil extracellular trap (NET) induction, disseminated intravascular coagulation, and inflammation. Understanding intracellular pathways that control platelet-neutrophil interactions is essential for identifying new therapeutic targets. Here, we found that thrombin signaling induced activation of the transcription factor NFAT in platelets. Using genetic and pharmacologic approaches, as well as iNFATuation, a newly developed mouse model in which NFAT activation can be abrogated in a cell-specific manner, we demonstrated that NFAT inhibition in activated murine and human platelets enhanced their activation and aggregation, as well as their interactions with neutrophils and NET induction. During gram-negative septicemia, NFAT inhibition in platelets promoted disease severity by increasing disseminated coagulation and NETosis. NFAT inhibition also partially restored coagulation ex vivo in patients with hypoactive platelets. Our results define non-transcriptional roles for NFAT that could be harnessed to address pressing clinical needs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.