IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade.
IL-21 is a Type I cytokine, which uses the common gamma chain (gamma(c)) in its receptor. As members of the gamma(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 gamma(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.
Ostiguy
Valérie
V
Department of Medicine, Maisonneuve-Rosemont Hospital Research Center, 5415 boul. de l'Assomption, University of Montreal, Montreal, Quebec, Canada HIT 2M4.
Allard
Eve-Line
EL
Marquis
Miriam
M
Leignadier
Julie
J
Labrecque
Nathalie
N
D000818:Animals; D015153:Blotting, Western; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects*; D004789:Enzyme Activation; D005434:Flow Cytometry; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D000098546:Interleukin-21
C508118:Il21r protein, mouse; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019869:Phosphatidylinositol 3-Kinases; D000098546:Interleukin-21