ArticleProceedings of the National Academy of Sciences of the United States of America2014
IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy.Oncoimmunology · 2026Review
- Regulatory T cells sabotage anti-tumor γδ T cells by creating IL-2-deficient environments.The Journal of experimental medicine · 2026Article
- NK cell cytotoxicity is transiently enhanced during acute malaria and modulated by the host microenvironment.JCI insight · 2026Article
- Engineered Mesenchymal Stem Cell-NK Cell Complexes for Spatially Targeted and Functionally Revitalized Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Innate immune dysregulation in celiac disease and refractory celiac disease: mechanisms, management and emerging therapies.Frontiers in immunology · 2026Review
- Article
- IL-15 transpresentation by ovarian cancer cells improves CD34Oncoimmunology · 2025Article
- Potentiating CAR-T cell function in the immunosuppressive tumor microenvironment by inverting the TGF-β signal.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Transpresentation of interleukin 15 by stromal cell subsets regulates immune cell homeostasis.Frontiers in immunology · 2025Article
- Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8Signal transduction and targeted therapy · 2024Article
- Cognate antigen-independent differentiation of resident memory T cells in chronic kidney disease.American journal of physiology. Renal physiology · 2024Article
- Comparative Evaluation of Synthetic Cytokines for Enhancing Production and Performance of NK92 Cell-Based Therapies.GEN biotechnology · 2023Article
- Nasal administration of recombinantJournal for immunotherapy of cancer · 2023Article
- Widespread and dynamic expression of granzyme C by skin-resident antiviral T cells.Frontiers in immunology · 2023Article
- Interleukin-15 enhanced the survival of human γδT cells by regulating the expression of Mcl-1 in neuroblastoma.Cell death discovery · 2022Article
- STAT5b: A master regulator of key biological pathways.Frontiers in immunology · 2022Review
- Engineering CAR-NK cells: how to tune innate killer cells for cancer immunotherapy.Immunotherapy advances · 2022Review
- Selective Targeting of IL-15Rα Is Sufficient to Reduce Inflammation.Frontiers in immunology · 2022Article
- IL-15Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy.Cellular & molecular immunology · 2021Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin (IL)-15 and its specific receptor chain, IL-15Rα, support the development of various effector cells, including NK and CD8 T cells via a mechanism called trans-presentation. Whereas the dynamic of trans-presentation has been shown to involve the recycling of IL-15Rα by presenting cells, the way responding cells integrate, or take advantage of this process has not been evaluated yet. To address this question, we set up a trans-presentation model using a membrane-bound IL-15.IL-15Rα fusion protein, and found that IL-15 is detectable within responding cells following IL-15 trans-presentation. The role of the proteolytic cleavage of IL-15Rα in this process was investigated by generating an uncleavable form of IL-15Rα. We showed that IL-15 entry into responding cells necessitates the cleavage of IL-15.IL-15Rα complex from the surface of IL-15 presenting cells, and observed that IL-15Rα cleavage is associated with a decrease of the duration of Stat5 signaling. Once separated from presenting cells, responding cells are able to recycle IL-15.IL-15Rα complexes via intracellular compartments, for residual proliferation in a time-limited manner. These studies define an unprecedented cytokine pathway in which the IL-15.IL-15Rα complex cleaved from presenting cells allows responding cells to internalize, store and use IL-15.IL-15Rα complex for their own proliferation and survival.
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