IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade

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Abstract
IL21 is a Type I cytokine, which uses the common γ chain (γc) in its receptor. As members of the γc cytokine/cytokine receptors family play crucial role in the differentiation, activation, and survival of lymphocytes, we have investigated if IL-21 could promote T cell survival and thus, contribute to T cell homeostasis and expansion. Unlike most γc cytokine receptors, we report that IL-21R is constitutively expressed by all mature T lymphocytes and that stromal cells of lymphoid organs are a constitutive source of IL-21. These observations are reminiscent of what is observed for IL-7/IL-7R, which control T cell survival and homeostasis and suggest a role for IL-21 in T cell homeostasis. Indeed, our results show that IL-21 is a survival factor for resting and activated T cells. Moreover, the ability of IL-21 to costimulate T cell proliferation is mediated by enhancing T cell viability. Further investigation of how IL-21R signaling induces T cell survival shows for the first time that IL-21 binding to its receptor activates the PI-3K signaling pathway and induces Bcl-2 expression. Moreover, the activation of the PI-3K signaling pathway is essential for IL-21-mediated T cell survival. Our data provide a new role for IL-21 in the immune system, which might be used to improve T cell homeostasis in immunocompromised patients.
Funding Information
  • Canadian Institutes of Health and Research (MOP-49499, NIP-67713)
  • Valorisation Recherche Québec
  • Guy-Bernier Research Center
  • FACS
  • CIHR (MME-67439)
  • CIHR