ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Cutting Edge: DNase II deficiency prevents activation of autoreactive B cells by double-stranded DNA endogenous ligands.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus.Science translational medicine · 2025Article
- Nucleic acid triggers of autoimmunity and autoinflammation.Current opinion in immunology · 2025Review
- Innate Immune Receptors as Dynamic Modulators of Extrafollicular Autoimmune B Cell Response.Immunological reviews · 2025Review
- Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.The Journal of experimental medicine · 2024Article
- Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases.Advances in experimental medicine and biology · 2024Article
- TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance.The Journal of experimental medicine · 2023Article
- Regulation of the nucleic acid-sensing Toll-like receptors.Nature reviews. Immunology · 2022Review
- TBK1 recruitment to STING mediates autoinflammatory arthritis caused by defective DNA clearance.The Journal of experimental medicine · 2022Article
- The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement.Frontiers in neurology · 2022Review
- Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy.Nature communications · 2021Article
- The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing.Frontiers in immunology · 2021Review
- Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids.Immunity · 2020Review
- Deoxyribonucleases and Their Applications in Biomedicine.Biomolecules · 2020Review
- Role of Interferon-γ-Producing Th1 Cells in a Murine Model of Type I Interferon-Independent Autoinflammation Resulting From DNase II Deficiency.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- The role of nucleic acid sensors and type I IFNs in patient populations and animal models of autoinflammation.Current opinion in immunology · 2019Review
- Review
- Self-DNA at the Epicenter of SLE: Immunogenic Forms, Regulation, and Effects.Frontiers in immunology · 2019Review
- Bacterial RNA Contributes to the Down-Modulation of MHC-II Expression on Monocytes/Macrophages Diminishing CD4Frontiers in immunology · 2019Article
- B. abortus RNA is the component involved in the down-modulation of MHC-I expression on human monocytes via TLR8 and the EGFR pathway.PLoS pathogens · 2017Article
- New Perspectives in Rheumatology: May You Live in Interesting Times: Challenges and Opportunities in Lupus Research.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In mice that fail to express the phagolysosomal endonuclease DNase II and the type I IFN receptor, excessive accrual of undegraded DNA results in a STING-dependent, TLR-independent inflammatory arthritis. These double-knockout (DKO) mice develop additional indications of systemic autoimmunity, including anti-nuclear autoantibodies and splenomegaly, that are not found in Unc93b1(3d/3d) DKO mice and, therefore, are TLR dependent. The DKO autoantibodies predominantly detect RNA-associated autoantigens, which are commonly targeted in TLR7-dominated systemic erythematosus lupus-prone mice. To determine whether an inability of TLR9 to detect endogenous DNA could explain the absence of dsDNA-reactive autoantibodies in DKO mice, we used a novel class of bifunctional autoantibodies, IgM/DNA dual variable domain Ig molecules, to activate B cells through a BCR/TLR9-dependent mechanism. DKO B cells could not respond to the IgM/DNA dual variable domain Ig molecule, despite a normal response to both anti-IgM and CpG ODN 1826. Thus, DKO B cells only respond to RNA-associated ligands because DNase II-mediated degradation of self-DNA is required for TLR9 activation.
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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.