ArticleProceedings of the National Academy of Sciences of the United States of America2012
Human macrophage and dendritic cell-specific silencing of high-mobility group protein B1 ameliorates sepsis in a humanized mouse model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Soluble RAGE enhances muscle regeneration after cryoinjury in aged and diseased mice.PloS one · 2025Article
- Dysregulated dendritic cells in sepsis: functional impairment and regulated cell death.Cellular & molecular biology letters · 2024Review
- Development of human innate immune responses in a humanized mouse model expressing four human myelopoiesis transgenes.Frontiers in immunology · 2024Article
- Upregulation of exosome secretion from tumor-associated macrophages plays a key role in the suppression of anti-tumor immunity.Cell reports · 2023Article
- Cell death proteins in sepsis: key players and modern therapeutic approaches.Frontiers in immunology · 2023Review
- Transcriptomic and ultrastructural evidence indicate that anti-HMGB1 antibodies rescue organic dust-induced mitochondrial dysfunction.Cell and tissue research · 2022Article
- Tanreqing Injection Attenuates Macrophage Activation and the Inflammatory ResponseFrontiers in immunology · 2022Article
- High Mobility Group Proteins in Sepsis.Frontiers in immunology · 2022Review
- Targeted Delivery of Nanovaccine to Dendritic Cells via DC-Binding Peptides Induces Potent Antiviral Immunity in vivo.International journal of nanomedicine · 2022Article
- HMGB1 as a therapeutic target in disease.Journal of cellular physiology · 2021Review
- Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021Review
- Inhibition of HMGB1 Might Enhance the Protective Effect of Taxifolin in Cardiomyocytes via PI3K/AKT Signaling Pathway.Iranian journal of pharmaceutical research : IJPR · 2021Article
- New Insights into the Immune System Using Dirty Mice.Journal of immunology (Baltimore, Md. : 1950) · 2020Review
- Review
- Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?ImmunoTargets and therapy · 2020Review
- Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Modeling Infectious Diseases in Mice with a "Humanized" Immune System.Microbiology spectrum · 2019Review
- The Fluctuations of Leukocytes and Circulating Cytokines in Septic Humanized Mice Vary With Outcome.Frontiers in immunology · 2019Article
- Transportan-derived cell-penetrating peptide delivers siRNA to inhibit replication of influenza virus in vivo.Drug design, development and therapy · 2019Article
- High-Mobility Group Box-1 and Liver Disease.Hepatology communications · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hypersecretion of cytokines by innate immune cells is thought to initiate multiple organ failure in murine models of sepsis. Whether human cytokine storm also plays a similar role is not clear. Here, we show that human hematopoietic cells are required to induce sepsis-induced mortality following cecal ligation and puncture (CLP) in the severely immunodeficient nonobese diabetic (NOD)/SCID/IL2Rγ(-/-) mice, and siRNA treatment to inhibit HMGB1 release by human macrophages and dendritic cells dramatically reduces sepsis-induced mortality. Following CLP, compared with immunocompetent WT mice, NOD/SCID/IL2Rγ(-/-) mice did not show high levels of serum HMGB1 or murine proinflammatory cytokines and were relatively resistant to sepsis-induced mortality. In contrast, NOD/SCID/IL2Rγ(-/-) mice transplanted with human hematopoietic stem cells [humanized bone marrow liver thymic mice (BLT) mice] showed high serum levels of HMGB1, as well as multiple human but not murine proinflammatory cytokines, and died uniformly, suggesting human cytokines are sufficient to induce organ failure in this model. Moreover, targeted delivery of HMGB1 siRNA to human macrophages and dendritic cells using a short acetylcholine receptor (AchR)-binding peptide [rabies virus glycoprotein (RVG)-9R] effectively suppressed secretion of HMGB1, reduced the human cytokine storm, human lymphocyte apoptosis, and rescued humanized mice from CLP-induced mortality. siRNA treatment was also effective when started after the appearance of sepsis symptoms. These results show that CLP in humanized mice provides a model to study human sepsis, HMGB1 siRNA might provide a treatment strategy for human sepsis, and RVG-9R provides a tool to deliver siRNA to human macrophages and dendritic cells that could potentially be used to suppress a variety of human inflammatory diseases.
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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.