ArticleJournal of immunology (Baltimore, Md. : 1950)2014
The transcription factor E4BP4 is not required for extramedullary pathways of NK cell development.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 55 citations in OpenAlex.
- Conserved functional features of natural killer cell subsets in chicken, human, and murine immune systems.iScience · 2025Article
- Group 1 ILCs: Heterogeneity, plasticity, and transcriptional regulation.Immunological reviews · 2024Review
- Inflammatory processes involved in NASH-related hepatocellular carcinoma.Bioscience reports · 2023Review
- SUMOylation and related post-translational modifications in natural killer cell anti-cancer responses.Frontiers in cell and developmental biology · 2023Review
- NK Cells and Other Cytotoxic Innate Lymphocytes in Colorectal Cancer Progression and Metastasis.International journal of molecular sciences · 2022Review
- Granzyme A and CD160 expression delineates ILC1 with graded functions in the mouse liver.European journal of immunology · 2021Article
- Natural killers or ILC1s? That is the question.Current opinion in immunology · 2021Review
- Review
- Transcriptional Regulation of Mouse Tissue-Resident Natural Killer Cell Development.Frontiers in immunology · 2020Review
- Shared Transcriptional Control of Innate Lymphoid Cell and Dendritic Cell Development.Annual review of cell and developmental biology · 2019Review
- Transcriptional control of natural killer cell differentiation.Immunology · 2019Review
- On the Way to Become a Natural Killer Cell.Frontiers in immunology · 2019Review
- Multiple Levels of Control Determine How E4bp4/Nfil3 Regulates NK Cell Development.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Article
- Dynamical Analysis of the Regulatory Network Controlling Natural Killer Cells Differentiation.Frontiers in physiology · 2018Article
- Adaptive NK cells can persist in patients withBlood · 2017Article
- Lacrimal Gland NK Cells Are Developmentally and Functionally Similar to Conventional NK Cells.ImmunoHorizons · 2017Article
- Transcriptional and post-transcriptional regulation of NK cell development and function.Clinical immunology (Orlando, Fla.) · 2017Review
- Epigenomic Views of Innate Lymphoid Cells.Frontiers in immunology · 2017Review
- Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
NK cells contribute to antitumor and antiviral immunosurveillance. Their development in the bone marrow (BM) requires the transcription factor E4BP4/NFIL3, but requirements in other organs are less well defined. In this study, we show that CD3(-)NK1.1(+)NKp46(+)CD122(+) NK cells of immature phenotype and expressing low eomesodermin levels are found in thymus, spleen, and liver of E4BP4-deficient mice, whereas numbers of mature, eomesodermin(high) conventional NK cells are drastically reduced. E4BP4-deficient CD44(+)CD25(-) double-negative 1 thymocytes efficiently develop in vitro into NK cells with kinetics, phenotype, and functionality similar to wild-type controls, whereas no NK cells develop from E4BP4-deficient BM precursors. In E4BP4/Rag-1 double-deficient (DKO) mice, NK cells resembling those in Rag-1-deficient controls are found in similar numbers in the thymus and liver. However, NK precursors are reduced in DKO BM, and no NK cells develop from DKO BM progenitors in vitro. DKO thymocyte precursors readily develop into NK cells, but DKO BM transfers into nude recipients and NK cells in E4BP4/Rag-1/IL-7 triple-KO mice indicated thymus-independent NK cell development. In the presence of T cells or E4BP4-sufficient NK cells, DKO NK cells have a selective disadvantage, and thymic and hepatic DKO NK cells show reduced survival when adoptively transferred into lymphopenic hosts. This correlates with higher apoptosis rates and lower responsiveness to IL-15 in vitro. In conclusion, we demonstrate E4BP4-independent development of NK cells of immature phenotype, reduced fitness, short t1/2, and potential extramedullary origin. Our data identify E4BP4-independent NK cell developmental pathways and a role for E4BP4 in NK cell homeostasis.
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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.