ArticleThe Journal of experimental medicine2005
A mutation in the Icsbp1 gene causes susceptibility to infection and a chronic myeloid leukemia-like syndrome in BXH-2 mice.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
- A novel dominant-negative variant of IRF8 in a mother and son: Clinical, phenotypic and biological characteristics.The Journal of allergy and clinical immunology · 2025Article
- Case Report: A patient with a novel heterozygous IRF8 variant with repeated infection and immune-mediated organ disease, but without disseminated mycobacterial disease despite BCG immunization.Frontiers in immunology · 2025Article
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- Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8.The Journal of experimental medicine · 2022Article
- The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis.Mucosal immunology · 2022Article
- The Roles of IRF-8 in Regulating IL-9-Mediated Immunologic Mechanisms in the Development of DLBCL: A State-of-the-Art Literature Review.Frontiers in oncology · 2022Review
- Mutation inFrontiers in immunology · 2021Article
- Generation and characterization of the Eµ-Irf8 mouse model.Cancer genetics · 2020Article
- Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases.Human genetics · 2020Review
- Article
- Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation.The Journal of allergy and clinical immunology · 2018Article
- Irf8 regulates the progression of myeloproliferative neoplasm-like syndrome via Mertk signaling in zebrafish.Leukemia · 2018Article
- IRF-8 regulates expansion of myeloid-derived suppressor cells and Foxp3+ regulatory T cells and modulates Th2 immune responses to gastrointestinal nematode infection.PLoS pathogens · 2017Article
- Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12 production.JCI insight · 2017Article
- Biallelic mutations in IRF8 impair human NK cell maturation and function.The Journal of clinical investigation · 2017Article
- Dendritic cell analysis in primary immunodeficiency.Current opinion in allergy and clinical immunology · 2016Review
- Relevance of Interferon Regulatory Factor-8 Expression in Myeloid-Tumor Interactions.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2016Review
- The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation.The Journal of experimental medicine · 2016Article
- Myeloid Growth Factors Promote Resistance to Mycobacterial Infection by Curtailing Granuloma Necrosis through Macrophage Replenishment.Cell host & microbe · 2015Article
- A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages.Genes & development · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
BXH-2 mice develop a fatal myeloid leukemia by a two-step mutagenic process. First, a BXH-2-specific recessive mutation causes a myeloproliferative syndrome. Second, retroviral insertions alter oncogenes or tumor suppressors, resulting in clonal expansion of leukemic cells. We have identified a recessive locus on chromosome 8 (Myls) that is responsible for myeloproliferation in BXH-2. This Myls interval has been narrowed down to 2 Mb and found to contain several positional candidates, including the interferon consensus sequence-binding protein 1 gene (Icsbp, also known as interferon regulatory factor 8 [IRF8]). We show that BXH-2 mice carry a mutation (915 C to T) resulting in an arginine-to-cysteine substitution at position 294 within the predicted IRF association domain of the protein. Although expression of Icsbp1 mRNA transcripts is normal in BXH-2 splenocytes, these cells are unable to produce interleukin 12 and interferon-gamma in response to activating stimuli, confirming that R294C behaves as a loss-of-function mutation. Myeloproliferation in BXH-2 mice is concomitant to increased susceptibility to Mycobacterium bovis (BCG) despite the presence of resistance alleles at the Nramp1 locus. These results suggest a two-step model for chronic myeloid leukemia in BXH-2, in which inactivation of Icsbp1 predisposes to myeloproliferation and immunodeficiency. This event is required for retroviral replication, and subsequent insertional mutagenesis that causes leukemia in BXH-2 mice.
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