ArticleJCI insight2021
IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Baseline Clinical Features and Biomarker Profiles of the Childhood Arthritis and Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease Cohort.Arthritis care & research · 2026Article
- Advances in pharmacotherapy for fibrotic interstitial lung disease.Medical review (2021) · 2026Review
- Article
- The "cytokine storm" in infection and sepsis: win the battle but lose the war.Military Medical Research · 2026Review
- Barrier Tissue-Resident Macrophages: Natural Compounds as Modulators in Immune Function and Disease.Current topics in medicinal chemistry · 2026Review
- EP9158H: An Immunoinformatics-Designed mRNA Vaccine Encoding Multi-Epitope Antigens and Dual TLR Agonists for Tuberculosis Prevention.Bioengineering (Basel, Switzerland) · 2025Article
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- Treating and triggering hyperinflammation: tackling hemophagocytic lymphohistiocytosis and HLH-like syndromes in the pediatric cell therapy and critical care setting.Frontiers in oncology · 2025Review
- Clinical characteristics and prognosis of interstitial lung disease in systemic juvenile idiopathic arthritis: a two-center retrospective observational cohort study.Pediatric rheumatology online journal · 2024Observational
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.Disease models & mechanisms · 2024Article
- Targeting the TRAF3-ULK1-NLRP3 regulatory axis to control alveolar macrophage pyroptosis in acute lung injury.Acta biochimica et biophysica Sinica · 2024Article
- The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome.bioRxiv : the preprint server for biology · 2024Article
- Single-cell RNA sequencing in juvenile idiopathic arthritis.Genes & diseases · 2024Review
- Heterogeneity of macrophage activation syndrome and treatment progression.Frontiers in immunology · 2024Review
- Population-level single-cell genomics reveals conserved gene programs in systemic juvenile idiopathic arthritis.The Journal of clinical investigation · 2023Article
- Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.Arthritis care & research · 2023Article
- Development of a Screening Algorithm for Lung Disease in Systemic Juvenile Idiopathic Arthritis.ACR open rheumatology · 2023Article
- Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome.Arthritis research & therapy · 2023Review
- Interferon with Dogma in Cytokine Release Syndrome and Acute Lung Injury.American journal of respiratory cell and molecular biology · 2023Article
- Increased Heme Oxygenase 1 Expression upon a Primary Exposure to the Respiratory Syncytial Virus and a SecondaryAntioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophage activation syndrome (MAS) is a life-threatening cytokine storm complicating systemic juvenile idiopathic arthritis (SJIA) driven by IFN-γ. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-γ pathways pathologically linking SJIA-LD and MAS. Our objective was to mechanistically define the potentially novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-γ, IFN-induced chemokines, and alveolar macrophage (AMϕ) expression of IFN-γ-induced genes. Single-cell RNA sequencing confirmed IFN-driven transcriptional changes across lung cell types with myeloid expansion and detection of MAS-specific macrophage populations. Systemic MAS resolution was associated with increased AMϕ and interstitial lymphocytic infiltration. AMϕ transcriptomic analysis confirmed IFN-γ-induced proinflammatory polarization during acute MAS, which switches toward an antiinflammatory phenotype after systemic MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and it reset AMϕ polarization toward a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-γ, both systemic features of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-γ-driven pulmonary inflammation replicating key features of SJIA-LD and provides a model system for testing potentially novel treatments directed toward SJIA-LD.
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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.