%0 Journal Article %T Cutting Edge: Differential Fine-Tuning of IL-2- and IL-15- Dependent Functions by targeting their Common IL-2/15Rβ/γc Receptor %+ Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA) %+ Centre hospitalier universitaire de Nantes (CHU Nantes) %+ Evitria [Schlieren, Suisse] %A Meghnem, Dihia %A Morisseau, Sébastien %A Frutoso, Marie %A Trillet, Kilian %A Maillasson, Mike %A Barbieux, Isabelle %A Khaddage, Sarah %A Leray, Isabelle %A Hildinger, Markus %A Quéméner, Agnès %A Jacques, Yannick %A Mortier, Erwan %Z This work was supported by CNRS, Inserm, Inserm Transfert (R13079NS) and was realized in the context of the Institut-Hospitalo Universitaire–Centre Europeen des Sciences de la Transplantation et Immunotherapies (ANR-10-IBHU-005) project, which received French government financial support managed by the National Research Agency and supported by Nantes Metropole and Pays de la Loire Region. D.M. was supported by a specific thesis allocation from the Institut-Hospitalo Universitaire–Centre Europeen des Sciences de la Transplantation et Immunotherapies. %< avec comité de lecture %@ 0022-1767 %J Journal of Immunology %I Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists %V 198 %N 12 %P 4563-4568 %8 2017-05-15 %D 2017 %R 10.4049/jimmunol.1700046 %M 28507024 %Z Life Sciences [q-bio]/CancerJournal articles %X Interleukin 2 and IL-15 are two closely related cytokines, displaying important functions in the immune system. They share the heterodimeric CD122/CD132 receptor to deliver their signals within target cells. Their specificity of action is conferred by their a receptor chains, IL-2Ra and IL-15Ra. By combining an increased affinity for CD122 and an impaired recruitment of CD132, we have generated an original molecule named IL-2Rb/g (CD122/CD132) inhibitor (BiG), targeting the CD122/CD132 receptor. BiG efficiently inhibited IL-15– and IL-2–dependent functions of primary cells, including CD8 T and NK cells, in vitro and in vivo. We also report a differential dynamic of action of these cytokines by highlighting a major role played by the IL-2Ra receptor. Interestingly, due to the presence of IL-2Ra, BiG had no impact on IL-2–dependent regulatory T cell proliferation. Thus, by acting as a fine switch in the immune system, BiG emphasizes the differential roles of these two cytokines. %G English %2 https://inserm.hal.science/inserm-01524397/document %2 https://inserm.hal.science/inserm-01524397/file/Jimmunol2017Eq1.pdf %L inserm-01524397 %U https://inserm.hal.science/inserm-01524397 %~ INSERM %~ UNIV-NANTES %~ CNRS %~ UNIV-ANGERS %~ CRCINA %~ ANR %~ NANTES-UNIVERSITE %~ UNIV-NANTES-AV2022