ArticleBlood2014
Transcription of the activating receptor NKG2D in natural killer cells is regulated by STAT3 tyrosine phosphorylation.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- Reconstitution of Natural Killer cells after allogeneic hematopoietic stem cell transplantation is facilitated by Huiyang-Guben decoction through activating the Smad7/Stat3 signal pathway.Molecular and cellular biochemistry · 2024Trial
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- Flavones and Aminoflavones Increase the Cytotoxicity of NK Cells in Human Non-Small Cell Lung Cancer.Journal of cellular and molecular medicine · 2026Article
- Targeting SHP-1-Mediated Inhibition of STAT3 and ERK Signalling Pathways Rescues the Hyporesponsiveness of MHC-I-Deficient NK-92MI.Cell proliferation · 2025Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- The effects of interleukin-21 in the biology of transplant rejection.Frontiers in immunology · 2025Review
- Melatonin enhances NK cell function in aged mice by increasing T-bet expression via the JAK3-STAT5 signaling pathway.Immunity & ageing : I & A · 2024Article
- Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.World journal of gastrointestinal oncology · 2024Article
- Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma.Journal for immunotherapy of cancer · 2024Article
- Exhausted signature and regulatory network of NK cells in myasthenia gravis.Frontiers in immunology · 2024Article
- Identification of m6A-associated LncRNAs as predict factors for the immune infiltration and prognosis of thyroid cancer.Annals of medicine · 2023Article
- Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death.Journal of cellular and molecular medicine · 2023Article
- Dynamic Changes in miRNA Expression during the Generation of Expanded and Activated NK Cells.International journal of molecular sciences · 2023Article
- Article
- The ups and downs of STAT3 function: too much, too little and human immune dysregulation.Clinical and experimental immunology · 2023Review
- Potentiation of natural killer cells to overcome cancer resistance to NK cell-based therapy and to enhance antibody-based immunotherapy.Frontiers in immunology · 2023Review
- JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.Frontiers in bioengineering and biotechnology · 2023Review
- Malignancy in STAT3 Deficient Hyper IgE Syndrome.Journal of clinical immunology · 2022Article
- Dichotomous effects of cellular expression of STAT3 on tumor growth of HNSCC.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Signal transducer and activator of transcription 3 (STAT3) is considered a negative regulator of inflammation, as inhibition of STAT3 signaling enhances antitumor immunity. However, STAT3 activation is a key oncogenic pathway in natural killer (NK)-lineage large granular lymphomas, and we recently reported enhanced proliferation and function of human NK cells activated with IL-21, which signals primarily through STAT3. These IL-21-expanded NK cells also have increased NKG2D expression, which led us to focus our investigation on whether STAT3 regulates NKG2D. In this study, we show that modulation of STAT3 phosphorylation with cytokines and small-molecule inhibitors correlates with NKG2D expression on human NK cells, leading to altered NK-cell degranulation. Moreover, NKG2D expression on murine NK cells having conditional STAT3 ablation is lower than on NK cells from wild-type mice, and human NK cells carrying dominant-negative STAT3 mutations have decreased baseline NKG2D expression and blunted responses to IL-10 and IL-21. Lastly, we show binding of STAT3 to a predicted STAT3 binding site upstream of the NKG2D gene, which is enhanced by IL-10 and IL-21 and decreased by STAT3 inhibition. Taken together, these data show that NKG2D expression in NK cells is regulated at the transcriptional level by STAT3, resulting in a functional NK cell defect in patients with STAT3 mutations.
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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.