ArticleThe Journal of clinical investigation2017
Biallelic mutations in IRF8 impair human NK cell maturation and function.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 100 citations in OpenAlex.
- Trial
- Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026Review
- PD-L1 is an intrinsic switch for natural killer cell-mediated, TRAIL-dependent antiviral function.Cell reports · 2026Article
- Bidirectional Mendelian Randomization Suggests Causal Effects of 731 Immunophenotypes on Vitiligo Pathogenesis.Clinical, cosmetic and investigational dermatology · 2026Article
- Tissue-specific antitumor NK cell subsets identified in colorectal cancer liver metastases express candidate therapeutic targets.The Journal of clinical investigation · 2025Article
- Interferon regulatory factor 8 expression and features in blastic plasmacytoid dendritic cell neoplasm and extranodal NK/T-cell lymphoma, nasal type.Histology and histopathology · 2025Article
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- 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
- Cutting Edge: Cooperative interferon regulatory factor network shapes the NK-cell antiviral response.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Expanding the phenotypic and genetic landscape of congenital neutropenia through whole-exome and genome sequencing.HemaSphere · 2025Article
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- CD11c-Cre driven deletion ofFrontiers in 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
- Brain abscess caused by Streptococcus pyogenes with atypical symptoms: a case report and literature review.BMC pediatrics · 2024Review
- The stress response regulator HSF1 modulates natural killer cell anti-tumour immunity.Nature cell biology · 2024Article
- Tissue-specific features of innate lymphoid cells in antiviral defense.Cellular & molecular immunology · 2024Review
- Genetic determinants and phenotypic consequences of blood T-cell proportions in 207,000 diverse individuals.Nature communications · 2024Article
- Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping.Nature immunology · 2024Article
- IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.Science advances · 2024Article
- FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.Cell · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 11 institutions in 3 countries.
Funding
Abstract
Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8-/-, but not Irf8+/-, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense.
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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.