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

Warren J. Leonard¹, Rong Zeng and Rosanne Spolski

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

¹ Correspondence: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bldg. 10, Rm. 7B05, Bethesda, MD 20892-1674, USA. E-mail: wil{at}helix.nih.gov

Interleukin-21 (IL-21) and its receptor represent the sixthcytokine system whose actions were recognized to require thecommon cytokine receptor ${gamma}$ chain. IL-21 is produced by activatedCD4⁺ T cells, natural killer T cells, and follicular T helpercells and has actions on a range of lymphohematopoietic lineages.Among its many effects, IL-21 serves a critical role for immunoglobulinproduction and terminal B cell differentiation, acts as a Tcell comitogen and can drive the expansion of CD8⁺ T cells,can negatively regulate dendritic cell function and plays anessential role in the differentiation of Th17 cells. Importantly,IL-21 is implicated in the pathogenesis of autoimmunity andexhibits potent actions as an antitumor agent. The ability toregulate and manipulate the actions of IL-21, therefore, hasimportant implications for immunoregulation and the therapyof human disease.