IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells
In: Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 (23), pp.8565. ⟨10.1073/pnas.1405514111⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2014, 111 (23), pp.8565. ⟨10.1073/pnas.1405514111⟩; (2014-05-27)
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Zugriff:
International audience; 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 cleav-age 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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IL-15.IL-15Rα complex shedding following trans-presentation is essential for the survival of IL-15 responding NK and T cells
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Autor/in / Beteiligte Person: | Jacques, Y. ; Nedellec, Steven ; Barbieux, Isabelle ; Tamzalit, Fella ; Morisseau, Sébastien ; Plet, Ariane ; Heim, Julie ; Mortier, Erwan ; Centre de Recherche en Cancérologie Nantes-Angers (CRCNA) ; Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes) ; Structure fédérative de recherche François Bonamy (SFR François Bonamy) ; Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN) |
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Quelle: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 (23), pp.8565. ⟨10.1073/pnas.1405514111⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2014, 111 (23), pp.8565. ⟨10.1073/pnas.1405514111⟩; (2014-05-27) |
Veröffentlichung: | National Academy of Sciences, 2014 |
Medientyp: | unknown |
ISSN: | 0027-8424 (print) ; 1091-6490 (print) |
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