ArticleThe Journal of experimental medicine2015
Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 164 citations in OpenAlex.
- Role of PRDM1 in natural killer cells.Molecular biology reports · 2026Review
- ID2 secures cDC1 specification by antagonizing E proteins at a pleiotropic Zeb2 enhancer.Nature immunology · 2026Article
- Transcription factors remodel tumor immune microenvironment by impacting multiple immune cells.Discover oncology · 2026Review
- The GFI1-FOXO1 axis regulates NK cell maturation and function.Nature communications · 2026Article
- CD127International journal of molecular sciences · 2026Article
- T-bet Fate Mapping Reveals Gestational Stage-Specific Transcriptional Adaptation of Decidual NK Cells.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Article
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- ID2 secures cDC1 specification by antagonizing E proteins at a pleiotropicResearch square · 2025Article
- Antigen specificity shapes distinct aging trajectories of memory CD8⁺ T cells.Nature communications · 2025Article
- In vivo AAV-SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy.Nature biotechnology · 2025Article
- Regulation of NK cell development, maturation, and antitumor responses by the nuclear receptor NR2F6.Cell death & disease · 2025Article
- Exosomal miR-552-5p Regulates the Role of NK Cells in EMT of Gastric Cancer via the PD-1/PD-L1 Axis.Journal of Cancer · 2025Article
- SLAMF7 defines subsets of human effector CD8 T cells.Scientific reports · 2024Article
- The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.Biomedicines · 2024Review
- Eomesodermin spatiotemporally orchestrates the early and late stages of NK cell development by targeting KLF2 and T-bet, respectively.Cellular & molecular immunology · 2024Article
- MEF2C regulates NK cell effector functions through control of lipid metabolism.Nature immunology · 2024Article
- No time to die: Epigenetic regulation of natural killer cell survival.Immunological reviews · 2024Review
- Identification, sorting and profiling of functional killer cells via the capture of fluorescent target-cell lysate.Nature biomedical engineering · 2024Article
- Heat shock protein gp96 drives natural killer cell maturation and anti-tumor immunity by counteracting Trim28 to stabilize Eomes.Nature communications · 2024Article
- The transcription factor ZEB2 drives the formation of age-associated B cells.Science (New York, N.Y.) · 2024Article
41 more citing papers are in PubMed but not listed here.
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23 authors at 10 institutions in 4 countries.
Funding
Abstract
Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells.
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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.