Cutting Edge: Differential Fine-Tuning of IL-2- and IL-15-Dependent Functions by Targeting Their Common IL-2/15Rβ/γc Receptor

The Journal of Immunology : Official Journal of the American Association of Immunologists
Dihia MeghnemErwan Mortier

Abstract

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 α receptor chains, IL-2Rα and IL-15Rα. By combining an increased affinity for CD122 and an impaired recruitment of CD132, we have generated an original molecule named IL-2Rβ/γ (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-2Rα receptor. Interestingly, due to the presence of IL-2Rα, 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.

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Citations

Jan 17, 2019·Annual Review of Immunology·Jian-Xin Lin, Warren J Leonard
Nov 20, 2019·Journal of Cellular and Molecular Medicine·Man ZhuWeina Ma
May 15, 2020·Journal of Cellular and Molecular Medicine·Lei GuoJian-An Wang
Dec 29, 2020·Journal of Cosmetic Dermatology·Mona A AtwaRadwa El-Sayed Mahmoud Marie
Jul 7, 2021·PLoS Pathogens·Fredrik BarrenäsMichael Gale
Jul 20, 2018·Science Translational Medicine·Jillian M RichmondJohn E Harris

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