ArticleProceedings of the National Academy of Sciences of the United States of America2020
Dysregulation of TLR9 in neonates leads to fatal inflammatory disease driven by IFN-γ.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 48 citations in OpenAlex.
- Phloretin Modulates STING Ubiquitination Degradation to Restrain Dendritic Cell Overactivation and Alleviate Sjögren's Syndrome.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Mitochondrial dysfunction in neonatal brain injury: from molecular mechanisms to therapeutic interventions.Journal of translational medicine · 2026Review
- Dual Targeting of TLR9 and cGAS-STING Pathways Attenuates Astrocyte Inflammatory Activation: Potential Implication in Multiple Sclerosis.Neurochemical research · 2025Article
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- The path ahead for understanding Toll-like receptor-driven systemic autoimmunity.Current opinion in immunology · 2024Review
- S100A8/A9-activated IFNγCellular and molecular life sciences : CMLS · 2024Article
- Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.The Journal of experimental medicine · 2024Article
- Murine Models of Secondary Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- DNA-Dependent Interferon Induction and Lung Inflammation inJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Identification of the immune-related biomarkers in Behcet's disease by plasma proteomic analysis.Arthritis research & therapy · 2023Article
- Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation.Bone research · 2022Article
- Regulation of the nucleic acid-sensing Toll-like receptors.Nature reviews. Immunology · 2022Review
- N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling.Frontiers in immunology · 2022Article
- Regulation of myeloid-cell activation.Current opinion in immunology · 2021Review
- [Mechanism and material basis ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- IL-27 Mediates Pro-Inflammatory EffectsFrontiers in immunology · 2021Article
- The Trinity of cGAS, TLR9, and ALRs Guardians of the Cellular Galaxy Against Host-Derived Self-DNA.Frontiers in immunology · 2020Review
- The association between poverty and gene expression within peripheral blood mononuclear cells in a diverse Baltimore City cohort.PloS one · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Recognition of self-nucleic acids by innate immune receptors can lead to the development of autoimmune and/or autoinflammatory diseases. Elucidating mechanisms associated with dysregulated activation of specific receptors may identify new disease correlates and enable more effective therapies. Here we describe an aggressive in vivo model of Toll-like receptor (TLR) 9 dysregulation, based on bypassing the compartmentalized activation of TLR9 in endosomes, and use it to uncover unique aspects of TLR9-driven disease. By inducing TLR9 dysregulation at different stages of life, we show that while dysregulation in adult mice causes a mild systemic autoinflammatory disease, dysregulation of TLR9 early in life drives a severe inflammatory disease resulting in neonatal fatality. The neonatal disease includes some hallmarks of macrophage activation syndrome but is much more severe than previously described models. Unlike TLR7-mediated disease, which requires type I interferon (IFN) receptor signaling, TLR9-driven fatality is dependent on IFN-γ receptor signaling. NK cells are likely key sources of IFN-γ in this model. We identify populations of macrophages and Ly6C
Indexed as
Identifiers
What OpenQuestion holds
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.