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Interleukin 21: a cytokine/cytokine receptor system that has come of age

Interleukin‐21 (IL‐21) and its receptor represent the sixth cytokine system whose actions were recognized to require the common cytokine receptor γ chain. IL‐21 is produced by activated CD4+ T cells, natural killer T cells, and follicular T helper cells and has actions on a range of lymphohematopoietic lineages. Among its many effects, IL‐21 serves a critical role for immunoglobulin production and terminal B cell differentiation, acts as a T cell comitogen and can drive the expansion of CD8+ T cells, can negatively regulate dendritic cell function and plays an essential role in the differentiation of Th17 cells. Importantly, IL‐21 is implicated in the pathogenesis of autoimmunity and exhibits potent actions as an antitumor agent. The ability to regulate and manipulate the actions of IL‐21, therefore, has important implications for immunoregulation and the therapy of human disease.