Interleukin-21: basic biology and implications for cancer and autoimmunity.
Interleukin-21 (IL-21), a potent immunomodulatory four-alpha-helical-bundle type I cytokine, is produced by NKT and CD4(+) T cells and has pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8(+) T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Conversely, IL-21 also has direct inhibitory effects on the antigen-presenting function of dendritic cells and can be proapoptotic for B cells and NK cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. The regulatory activity of IL-21 is modulated by the differentiation state of its target cells as well as by other cytokines or costimulatory molecules. IL-21 has potent antitumor activity but is also associated with the development of autoimmune disease. IL-21 transcription is dependent on a calcium signal and NFAT sites, and IL-21 requires Stat3 for its signaling. The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor.
Spolski
Rosanne
R
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892-1674, USA. spolskir@nhlbi.nih.gov
Leonard
Warren J
WJ
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000098546:Interleukin-21
D007378:Interleukins; D000098546:Interleukin-21