ArticleeLife2017
High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 86 citations in OpenAlex.
- Review of the Effects of Anesthetic Techniques and Medications on the Immune Response During the Perioperative Period.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.Cell reports. Medicine · 2026Article
- Metabolism-driven posttranslational modifications and immune regulation: Emerging targets for immunotherapy.Science advances · 2025Review
- LAG3 Marks Activated but Hyporesponsive NK Cells.European journal of immunology · 2025Article
- Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality.Journal for immunotherapy of cancer · 2025Article
- Tumor-induced natural killer cell dysfunction is a rapid and reversible process uncoupled from the expression of immune checkpoints.Science advances · 2024Article
- Egr2 to the rescue: nanoparticles revitalize natural killer cells in the fight against cancer.The EMBO journal · 2024Article
- NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Multifactorial determinants of NK cell repertoire organization: insights into age, sex, KIR genotype, HLA typing, and CMV influence.Frontiers in immunology · 2024Article
- Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.Blood advances · 2023Article
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection.Nature communications · 2023Article
- Destined for the intestine: thymic selection of TCRαβ CD8αα intestinal intraepithelial lymphocytes.Clinical and experimental immunology · 2023Review
- 25KDa branched polyethylenimine increases interferon-γ production in natural killer cells via improving translation efficiency.Cell communication and signaling : CCS · 2023Article
- Understanding NK cell biology for harnessing NK cell therapies: targeting cancer and beyond.Frontiers in immunology · 2023Review
- The cellular triumvirate: fibroblasts entangled in the crosstalk between cancer cells and immune cells.Frontiers in immunology · 2023Review
- Preventing Surgery-Induced NK Cell Dysfunction Using Anti-TGF-β Immunotherapeutics.International journal of molecular sciences · 2022Article
- Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.The Journal of experimental medicine · 2022Article
- Altered-Self MHC Class I Sensing via Functionally Disparate Paired NK Cell Receptors Counters Murine Cytomegalovirus gp34-Mediated Immune Evasion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate.Cancer immunology research · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK cell education is the process through which chronic engagement of inhibitory NK cell receptors by self MHC-I molecules preserves cellular responsiveness. The molecular mechanisms responsible for NK cell education remain unclear. Here, we show that mouse NK cell education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to the number of educating receptors. This higher activity was dependent on the SHP-1 phosphatase and essential for the improved responsiveness of reactive NK cells. Upon stimulation, the mTOR/Akt pathway amplified signaling through activating NK cell receptors by enhancing calcium flux and LFA-1 integrin activation. Pharmacological inhibition of mTOR resulted in a proportional decrease in NK cell reactivity. Reciprocally, acute cytokine stimulation restored reactivity of hyporesponsive NK cells through mTOR activation. These results demonstrate that mTOR acts as a molecular rheostat of NK cell reactivity controlled by educating receptors and uncover how cytokine stimulation overcomes NK cell education.
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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.