ArticleThe Journal of clinical investigation2007
NK cell survival mediated through the regulatory synapse with human DCs requires IL-15Ralpha.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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
55 citing papers in PubMed, 97 citations in OpenAlex.
- Trial
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?Frontiers in immunology · 2023Review
- Emerging NK cell therapies for cancer and the promise of next generation engineering of iPSC-derived NK cells.Journal for immunotherapy of cancer · 2022Review
- Natural Killer-Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy.Cancers · 2021Review
- Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.Frontiers in immunology · 2021Review
- Review
- Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation.Blood advances · 2020Article
- Complement-activated interferon-γ-primed human endothelium transpresents interleukin-15 to CD8+ T cells.The Journal of clinical investigation · 2020Article
- Connexin-Mediated Signaling at the Immunological Synapse.International journal of molecular sciences · 2020Review
- Article
- Review
- Dendritic Cell-Derived IL-32α: A Novel Inhibitory Cytokine of NK Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors.EMBO molecular medicine · 2016Article
- Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation.Nature neuroscience · 2016Article
- NK Cell Proliferation Induced by IL-15 Transpresentation Is Negatively Regulated by Inhibitory Receptors.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- NK cell activation in human hantavirus infection explained by virus-induced IL-15/IL15Rα expression.PLoS pathogens · 2014Article
- Phenotypic and functional activation of hyporesponsive KIRnegNKG2Aneg human NK-cell precursors requires IL12p70 provided by Poly(I:C)-matured monocyte-derived dendritic cells.Cancer immunology research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to protect mature DCs from NK cell lysis, the NK cell also received activation signals that induced mobilization of intracellular calcium and CD69 upregulation. The high-affinity component of the receptor for IL-15, IL-15Ralpha, accumulated at the synapse center on NK cells, and blocking of IL-15Ralpha increased NK cell apoptosis and diminished NK cell survival during their interaction with DCs. Furthermore, IL-15Ralpha-deficient NK cells, obtained from donors with a history of infectious mononucleosis, showed diminished survival in culture with DCs. Synapse formation was required for IL-15Ralpha-mediated NK cell survival, because synapse disruption by adhesion molecule blocking decreased DC-induced NK cell survival. These results identify what we believe to be a novel regulatory NK cell synapse with hallmarks of spatially separated inhibitory and activating interactions at its center. We suggest that this synapse formation enables optimal NK cell activation by DCs during innate immune responses.
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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.