Interleukin-21: a multifunctional regulator of immunity to infections - PubMed (original) (raw)

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Interleukin-21: a multifunctional regulator of immunity to infections

John S Yi et al. Microbes Infect. 2010 Dec.

Abstract

Interleukin-21 (IL-21) is a cytokine that has broad effects on both innate and adaptive immune responses. The roles of IL-21 in determining immunity to infections are currently being defined, and notably, it has been shown that IL-21 is most critical for sustaining T cell responses during chronic viral infections. This article discusses our current understanding of the immunobiology of IL-21, as well as its known and potential roles in influencing immunity to infections.

Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

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Figures

Figure 1

Figure 1

The sources of IL-21. Both NKT cells and CD4 T cells have been shown to produce IL-21. Within the CD4 T cell population, Th17 and Tfh are the most prominent producers, whereas IL-21 is not secreted by CD4 Treg cells. CD8 T cell responses are not commonly associated with IL-21 production, although a limited number of studies indicate that this can occur.

Figure 2

Figure 2

The influence of IL-21 on the differentiation, function, and survival of cells of the immune system. IL-21 enhances the function of macrophages, NK, and NKT cells. It also supports the formation of germinal center B cells and the generation of plasma cells. IL-21 promotes the differentiation of Th17 cells and sustains Tfh responses but inhibits the development of Tregs. Additionally, IL-21 can restrict the maturation of DCs and may limit the differentiation of effector CD8 T cells.

Figure 3

Figure 3

CD4 T cell responses are a major determinant of IL-21 levels, which influence the quality of the CD8 T cell response and the control of viral infections. A. Acute viral infections commonly elicit IFN-γ and IL-21 producing CD4 T cell responses. This is associated with robust effector CD8 T cell responses, memory formation, and control of the infection. B and C. Disruptions to the numbers and/or functional quality of CD4 T cell responses can result in diminished levels of IL-21 producing cells, especially during the early stage of infection. In these circumstances, higher levels of virus replication, ablated CD4 T cell responses, as well as limited availability of IL-21 all likely contribute to impaired CD8 T cell responses and ineffective viral clearance.

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References

    1. Mehta DS, Wurster AL, Grusby MJ. Biology of IL-21 and the IL-21 receptor. Immunol Rev. 2004;202:84–95. - PubMed
    1. Spolski R, Leonard WJ. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol. 2008;26:57–79. - PubMed
    1. Ozaki K, Kikly K, Michalovich D, Young PR, Leonard WJ. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci U S A. 2000;97:11439–11444. - PMC - PubMed
    1. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57–63. - PubMed
    1. Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K. Cuttin edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol. 2001;167:1–5. - PubMed

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