ArticleThe Journal of clinical investigation2011
Repeated TLR9 stimulation results in macrophage activation syndrome-like disease in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers, 3 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
213 citing papers in PubMed, 3 syntheses or guidelines pooled it, 382 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Update in Hyperferritinemic Syndromes: Recognition and Management - A Scoping Review.The Brown journal of hospital medicine · 2022Pooled it
- Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis.Journal of clinical immunology · 2020Pooled it
- Metabolomics of in vivo inflammation identifies soluble sialic acid as a conserved myeloid-cell metabolite.The Journal of biological chemistry · 2026Article
- A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation.Nature chemical biology · 2026Article
- Loss of IL10 Signaling Promotes TLR9-Driven Liver Dysfunction by Allowing T Cell Receptor-Mediated T Cell Activation.Research square · 2026Article
- A Review of Hemophagocytic Lymphohistiocytosis in Transplant-Focusing on the Heart.Clinical transplantation · 2026Review
- Metabolomics ofbioRxiv : the preprint server for biology · 2026Article
- Type I Interferon-Driven Monocyte Dysregulation and MAS-associated CD8bioRxiv : the preprint server for biology · 2026Article
- Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling.The Journal of cell biology · 2026Article
- STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation.JHEP reports : innovation in hepatology · 2026Article
- TLR9 decreases FOXO3 expression to prevent excessive inflammation in macrophage activation syndrome.iScience · 2025Article
- Impact of Interleukin-1 Blockade on the Development of Macrophage Activation Syndrome in Still Disease: Incidence and Diagnostic Validity of the EULAR/ACR/PRINTO 2016 MAS Classification Criteria.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections.Nature biomedical engineering · 2025Article
- Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Monocyte/macrophages may exert prominent roles in macrophage activation syndrome.Annals of hematology · 2025Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- The clinical features and outcomes of aggressive large B cell lymphoma with concomitant hemophagocytic lymphohistiocytosis at diagnosis.Annals of hematology · 2025Article
- Fatal Cytokine Collision: HLH-AIHA in Advanced AIDS-Case Report and Literature Review.Reports (MDPI) · 2025Article
153 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are 2 similar diseases characterized by a cytokine storm, overwhelming inflammation, multiorgan dysfunction, and death. Animal models of HLH suggest that disease is driven by IFN-γ produced by CD8⁺ lymphocytes stimulated by persistent antigen exposure. In these models and patients with "primary" HLH, the antigen persists due to genetic defects, resulting in ineffective cytotoxic responses by CD8⁺ T cells and poor pathogen clearance. However, infectious triggers are often not identified in patients with MAS, and some patients with HLH or MAS lack defects in cytotoxic T cell killing. Herein, we show that repeated stimulation of TLR9 produced an HLH/MAS-like syndrome on a normal genetic background, without exogenous antigen. Like previous HLH models, TLR9-induced MAS was IFN-γ dependent; however, unlike other models, disease did not require lymphocytes. We further showed that IL-10 played a protective role in this model and that blocking IL-10 signaling led to the development of hemophagocytosis. IL-10 may therefore be an important target for the development of effective therapeutics for MAS. Our data provide insight into MAS-like syndromes in patients with inflammatory diseases in which there is chronic innate immune activation but no genetic defects in cytotoxic cell function.
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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.