| Different dynamics of IL-15R activation following IL-15 cis- or trans-presentation. | |
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MedLine Citation:
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PMID: 21078585 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function of NK cells, NK-T cells, and memory CD8+ T cells. IL-15 signals are delivered through the IL-15Rβ and the common γ (γ(c)) receptor chains. The third receptor chain, IL-15Rα, confers specificity and high affinity for the cytokine. While IL-15 can activate with high affinity the trimeric receptor expressed by a target cell (cis-presentation), IL-15Rα is also known to trans-present IL-15 with high affinity to target cells expressing the IL-15Rβ/γ(c) complex. In order to compare the IL-15 cis- and trans-presentation processes, and using a T cell line expressing both IL-15Rα/β/γ(c) and IL-15Rβ/γ(c), we analyzed cell surface receptor chain down-modulation, cytokine internalization and signaling responses induced either with IL-15 (cis-presentation) or with RLI, a protein resulting from fusion between IL-15 and an extended IL-15Rα sushi domain, that mimics trans-presentation. Whereas IL-15 bound with high affinity to IL-15Rα/β/γ(c), RLI bound with a similar high affinity to IL-15Rβ/γ(c). The kinetics of cell surface IL-15R down-modulation were slower following RLI treatment than after IL-15 treatment, as were the kinetics of RLI internalization, which was slower than that of IL-15. IL-15 and RLI dose-dependently induced the activation of similar signaling pathways. However, the kinetics and duration of these activations were markedly different, RLI-induced signaling, being slower, but more prolonged than that induced by IL-15, although the final proliferative responses at 48 h were similar. These findings collectively indicate that IL-15 cis- and trans-presentation mechanisms lead to different dynamics of receptor activation and signal transduction, with cis-presentation inducing fast and transient responses, and trans-presentation inducing slower, more persistent ones. They provide clues for a better understanding of how IL-15 action is controlled, and how it plays a key role in the coordination between innate and adaptative immunity. |
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Authors:
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Harmonie Perdreau; Erwan Mortier; Grégory Bouchaud; Véronique Solé; Yvan Boublik; Ariane Plet; Yannick Jacques |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-16 |
Journal Detail:
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Title: European cytokine network Volume: 21 ISSN: 1148-5493 ISO Abbreviation: Eur. Cytokine Netw. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-17 Completed Date: 2011-10-14 Revised Date: 2012-01-05 |
Medline Journal Info:
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Nlm Unique ID: 9100879 Medline TA: Eur Cytokine Netw Country: France |
Other Details:
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Languages: eng Pagination: 297-307 Citation Subset: IM |
Affiliation:
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INSERM UMR 892, Centre de Recherche en Cancérologie Nantes/Angers, Groupe de Recherche Cytokines et Récepteurs en Immuno-Cancérologie, Nantes, France. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigen Presentation
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immunology* Cell Line, Tumor Gene Expression Regulation* / drug effects Humans Interleukin-15 / immunology*, pharmacology Lymphocyte Activation* / drug effects Receptors, Interleukin-15 / immunology* Recombinant Fusion Proteins / immunology, metabolism, pharmacology Signal Transduction* / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-15; 0/Receptors, Interleukin-15; 0/Recombinant Fusion Proteins |
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