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Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity*

Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity* Interleukin-21 (IL-21), a potent immunomodulatory four-α-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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Immunology Annual Reviews

Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity*

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Publisher
Annual Reviews
Copyright
Copyright © 2008 by Annual Reviews. All rights reserved
ISSN
0732-0582
eISSN
1545-3278
DOI
10.1146/annurev.immunol.26.021607.090316
pmid
17953510
Publisher site
See Article on Publisher Site

Abstract

Interleukin-21 (IL-21), a potent immunomodulatory four-α-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.

Journal

Annual Review of ImmunologyAnnual Reviews

Published: Apr 23, 2008

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