ArticleBlood2016
ST2 contributes to T-cell hyperactivation and fatal hemophagocytic lymphohistiocytosis in mice.
Article in Blood, 2016. 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, 65 citations in OpenAlex.
- Unlocking IL-33: New Insights into Tumor Immunity.Immune network · 2025Review
- Promising Targeted Therapies for Hemophagocytic Lymphohistiocytosis: A Translational Perspective Based on Immunopathology.Clinical reviews in allergy & immunology · 2025Review
- Tislelizumab-induced hemophagocytic lymphohistiocytosis in a patient with microsatellite instability-high colon cancer and coexisting systemic lupus erythematosus: a case report and literature review.Frontiers in oncology · 2025Article
- Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect.The Journal of experimental medicine · 2024Article
- Elevation of IL-17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- A type 1 immunity-restricted promoter of the IL-33 receptor gene directs antiviral T-cell responses.Nature immunology · 2024Article
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- IL-1 Family Blockade in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Cytokine Storm Syndrome Associated with Systemic Juvenile Idiopathic Arthritis.Advances in experimental medicine and biology · 2024Review
- Cytokine Storm Syndromes Associated with Epstein-Barr Virus.Advances in experimental medicine and biology · 2024Review
- CD8Advances in experimental medicine and biology · 2024Review
- Cytokines in Cytokine Storm Syndrome.Advances in experimental medicine and biology · 2024Review
- Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- CXCL9 inhibition does not ameliorate disease in murine models of both primary and secondary hemophagocytic lymphohistiocytosis.Scientific reports · 2023Article
- The hyperinflammatory spectrum: from defects in cytotoxicity to cytokine control.Frontiers in immunology · 2023Review
- The Role of the IL-33/ST2 Axis in CpG-Induced Macrophage Activation Syndrome.Journal of immunology research · 2023Article
- Familial hemophagocytic lymphohistiocytosis hepatitis is mediated by IFN-γ in a predominantly hepatic-intrinsic manner.PloS one · 2022Article
- Targeting interferon-γ in hyperinflammation: opportunities and challenges.Nature reviews. Rheumatology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cytokine storm syndromes, such as familial hemophagocytic lymphohistiocytosis (FHL), are lethal disorders caused by uncontrolled, systemic immune activation. In the murine model of FHL, in which perforin-deficient (Prf1(-/-)) mice are infected with lymphocytic choriomeningitis virus (LCMV), disease is driven by overabundant interferon (IFN)γ-producing LCMV-specific CD8(+) T cells thought to arise from excessive antigen stimulation through the T-cell receptor. However, this paradigm is insufficient to explain several fundamental aspects of FHL, namely, the inability of many pathogenic antigens to induce hyperinflammation, and the previously identified role of MyD88 in the disease. We now show a novel role for the MyD88-dependent interleukin-33 (IL-33) receptor, ST2, in FHL. Expression of IL-33 and ST2 is upregulated in LCMV-infected Prf1(-/-) mice. Blockade of ST2 markedly improves survival of LCMV-infected Prf1(-/-) mice and reduces the severity of multiple disease parameters, including serum levels of IFNγ. This decrease in IFNγ corresponds to a reduction in both the frequency of IFNγ(+) LCMV-specific CD8(+) and CD4(+) T cells and the magnitude of IFNγ expression in these cells. These findings demonstrate that disruption of ST2 signaling in the murine model of FHL reduces T cell-mediated production of IFNγ and suggest a revised paradigm in which danger signals such as IL-33 are crucial amplifiers of immune dysregulation in FHL. Furthermore, this study provides evidence to support blockade of ST2 as a novel therapeutic strategy for FHL.
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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.