ArticleArthritis & rheumatology (Hoboken, N.J.)2019
Brief Report: Interferon-γ-Mediated Immunopathology Potentiated by Toll-Like Receptor 9 Activation in a Murine Model of Macrophage Activation Syndrome.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- Monocyte/macrophages may exert prominent roles in macrophage activation syndrome.Annals of hematology · 2025Article
- Secreted ISG15 induced by Chlamydia trachomatis infection exerts immunomodulatory effects on IFN-γ defense and inflammation.PLoS pathogens · 2025Article
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- JAK Inhibitors in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- The Liver in Hemophagocytic Lymphohistiocytosis: Not an Innocent Bystander.Journal of pediatric gastroenterology and nutrition · 2023Review
- CXCL9 inhibition does not ameliorate disease in murine models of both primary and secondary hemophagocytic lymphohistiocytosis.Scientific reports · 2023Article
- Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome.Arthritis research & therapy · 2023Review
- Electroacupuncture Alleviates Lung Injury in CpG1826-Challenged Mice via Modulating CD39-NLRP3 Pathway.Journal of inflammation 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
- Cleavage of DNA and RNA by PLD3 and PLD4 limits autoinflammatory triggering by multiple sensors.Nature communications · 2021Article
- IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome.JCI insight · 2021Article
- Amelioration of Murine Macrophage Activation Syndrome by Monomethyl Fumarate in Both a Heme Oxygenase 1-Dependent and Heme Oxygenase 1-Independent Manner.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- The Pathogenic Role of Interferons in the Hyperinflammatory Response on Adult-Onset Still's Disease and Macrophage Activation Syndrome: Paving the Way towards New Therapeutic Targets.Journal of clinical medicine · 2021Review
- Dysregulation of TLR9 in neonates leads to fatal inflammatory disease driven by IFN-γ.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interferon target-gene expression and epigenomic signatures in health and disease.Nature immunology · 2019Review
- A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.Nature communications · 2019Article
- TLR7 Agonism Accelerates Disease and Causes a Fatal Myeloproliferative Disorder in NZM 2410 Lupus Mice.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveMacrophage activation syndrome (MAS) is a life-threatening cytokine storm syndrome that occurs in patients with underlying rheumatic diseases. Preclinical and clinical data suggest that interferon-γ (IFNγ) is pathogenic in MAS, but how IFNγ may be linked to disease pathogenesis remains unknown. This study was undertaken to determine whether IFNγ signals synergize with systemic innate immune responses to drive the cytokine storm in a murine model of MAS.
methodsIFNγ-deficient mice were treated with 5 doses of the Toll-like receptor 9 (TLR-9) agonist CpG 1826, IFNγ, or a combination of the 2 stimuli over the course of 10 days. Immunopathologic features of MAS, including cytopenias, hepatitis, hepatosplenomegaly, and induction of inflammatory myelopoiesis, were assessed. Mixed bone marrow chimeras were created to determine whether TLR-9- and IFNγ receptor 1 (IFNγR1)-dependent signals induce enhanced myelopoiesis in a cell-intrinsic or cell-extrinsic manner.
resultsIFNγ-deficient mice did not develop features of MAS when treated with repeated doses of either the TLR-9 agonist or IFNγ alone. In contrast, IFNγ-deficient mice treated with both the TLR-9 agonist and IFNγ developed cytopenias, hepatitis, and hepatosplenomegaly, reproducing major clinical features of MAS. TLR-9- and IFNγR1-dependent signals synergized to enhance myeloid progenitor cell function and induce myelopoiesis in vivo, which occurred through cell-extrinsic mechanisms and correlated with the induction of disease.
conclusionThese findings demonstrate that TLR-9-driven signals potentiate the effects of IFNγ to initiate murine MAS, and provide evidence that induction of inflammatory myelopoiesis is a common TLR-9- and IFNγ-dependent pathway that may contribute to the pathogenesis of MAS.
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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.