ArticleBlood2011
Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the γc cytokines and TGF-β1.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 109 citations in OpenAlex.
- Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis.PLoS neglected tropical diseases · 2026Article
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
- NKG2D ligand expression on NK cells induces NKG2D-mediated cross-tolerization of cytokine signaling and reduces NK cell tumor immunity.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives.Cancer metastasis reviews · 2024Review
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.Frontiers in immunology · 2024Article
- Immune evasion by proteolytic shedding of natural killer group 2, member D ligands inFrontiers in immunology · 2024Article
- The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy.International journal of molecular sciences · 2023Review
- Coordinated Priming of NKG2D Pathway by IL-15 Enhanced Functional Properties of Cytotoxic CD4Inflammation · 2023Article
- Preventing Surgery-Induced NK Cell Dysfunction Using Anti-TGF-β Immunotherapeutics.International journal of molecular sciences · 2022Article
- Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis.Digestive diseases and sciences · 2022Review
- Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions.Exploration of targeted anti-tumor therapy · 2022Review
- Revolution of CAR Engineering For Next-Generation Immunotherapy In Solid Tumors.Frontiers in immunology · 2022Review
- Expanded human NK cells armed with CAR uncouple potent anti-tumor activity from off-tumor toxicity against solid tumors.iScience · 2021Article
- Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future.Stem cell research & therapy · 2021Review
- NK Cell Adoptive Immunotherapy of Cancer: Evaluating Recognition Strategies and Overcoming Limitations.Transplantation and cellular therapy · 2021Review
- Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner.Frontiers in immunology · 2021Review
- Review
- Review
- Natural Killer Cell Responses in Hepatocellular Carcinoma: Implications for Novel Immunotherapeutic Approaches.Cancers · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells help protect the host against viral infections and tumors. NKG2D is a vital activating receptor, also expressed on subsets of T cells, whose ligands are up-regulated by cells in stress. Ligation of NKG2D leads to phosphorylation of the associated DAP10 adaptor protein, thereby activating immune cells. Understanding how the expression of NKG2D-DAP10 is regulated has implications for immunotherapy. We show that IL-2 and TGF-β1 oppositely regulate NKG2D-DAP10 expression by NK cells. IL-2 stimulation increases NKG2D surface expression despite a decrease in NKG2D mRNA levels. Stimulation with IL-2 results in a small increase of DAP10 mRNA and a large up-regulation of DAP10 protein synthesis, indicating that IL-2-mediated effects are mostly posttranscriptional. Newly synthesized DAP10 undergoes glycosylation that is required for DAP10 association with NKG2D and stabilization of NKG2D expression. TGF-β1 has an opposite and dominant effect to IL-2. TGF-β1 treatment decreases DAP10, as its presence inhibits the association of RNA polymerase II with the DAP10 promoter, but not NKG2D mRNA levels. This leads to the down-regulation of DAP10 expression and, as a consequence, NKG2D protein as well. Finally, we show that other γ(c) cytokines act similarly to IL-2 in up-regulating DAP10 expression and NKG2D-DAP10 surface expression.
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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.