ArticleThe Journal of experimental medicine2008
Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 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
53 citing papers in PubMed, 116 citations in OpenAlex.
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- Beyond Negative Regulation: IL-1R8 and IL-1R2 as Novel Immune Checkpoints.European journal of immunology · 2025Review
- Interleukin 38 alleviates aortic valve calcification by inhibition of NLRP3.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus.Journal of innate immunity · 2022Article
- Molecular characterization and functional analysis of DIGIRR from golden pompano (Frontiers in immunology · 2022Article
- Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.Frontiers in immunology · 2022Review
- Immune response against Chlamydia trachomatis via toll-like receptors is negatively regulated by SIGIRR.PloS one · 2020Article
- IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development.Cancer immunology research · 2019Article
- Increased ratio of Th17 cells to SIGIRRBiomedical reports · 2018Article
- Tuning inflammation and immunity by the negative regulators IL-1R2 and IL-1R8.Immunological reviews · 2018Review
- High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity.Oncotarget · 2017Article
- Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus Erythematosus Model.Frontiers in immunology · 2017Article
- Cytokine decoy and scavenger receptors as key regulators of immunity and inflammation.Cytokine · 2016Article
- Regulatory Role of IL-1R8 in Immunity and Disease.Frontiers in immunology · 2016Review
- Roles of B Cell-Intrinsic TLR Signals in Systemic Lupus Erythematosus.International journal of molecular sciences · 2015Review
- The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity.Molecular biology reports · 2015Article
- Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation.Nature immunology · 2014Article
- Emerging role of SIGIRR rs7396562(T/G) polymorphism in systemic lupus erythematosus in a Chinese population.Inflammation · 2014Article
- Pattern recognition receptors and the inflammasome in kidney disease.Nature reviews. Nephrology · 2014Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4(+)CD25(+) T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice.
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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.