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IL‐21 promotes T lymphocyte survival by activating the phosphatidylinositol‐3 kinase signaling cascade
Author(s) -
Ostiguy Valérie,
Allard ÈveLine,
Marquis Miriam,
Leignadier Julie,
Labrecque Nathalie
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0806494
Subject(s) - biology , microbiology and biotechnology , cytokine , t cell , signal transduction , il 2 receptor , common gamma chain , receptor , homeostasis , immune system , immunology , interleukin 10 , biochemistry
IL21 is a Type I cytokine, which uses the common γ chain (γ c ) in its receptor. As members of the γ c 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 γ c 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.