alexa The Emerging Role of Interleukin-21 in Transplantation
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
Open Access

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Review Article

The Emerging Role of Interleukin-21 in Transplantation

Aini Xie1,2, Eric Dale Buras1, Jiahong Xia2* and Wenhao Chen1*
1Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA
2Department of Cardiovascular Surgery, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
Corresponding Authors : Wenhao Chen
Division of Diabetes, Endocrinology and Metabolism
Department of Medicine, Baylor College of Medicine
One Baylor Plaza (MS: BCM185), Houston, TX, 77030, USA
Tel: 713-798-1698
Fax: 713-798-4575
E-mail: [email protected]
  Jiahong Xia
Department of Cardiovascular Surgery
Union Hospital, Huazhong University of Science and Technology
Wuhan Jiefang Road 1277#, Wuhan, Hubei, 430022, China
Tel: 0086-13971038472
Fax: 0086-27-85355457
E-mail:[email protected]
Received June 18, 2012; Accepted August 18, 2012; Published August 24, 2012
Citation: Xie A, Buras ED, Xia J, Chen W (2012) The Emerging Role of Interleukin-21 in Transplantation. J Clin Cell Immunol S9:002. doi:10.4172/2155-9899.S9-002
Copyright: © 2012 Xie A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Since its discovery in 2000, IL-21 has been shown to play critical roles in the regulation of both innate and adaptive immune responses. IL-21 is produced predominantly by multiple effector CD4+ T-cell types [T helper 17 (Th17), follicular helper T (TFH), and other activated CD4+ cells] and NKT cells. In addition to T cell receptor (TCR) signals, the production of IL-21 by activated CD4+ T cells is intricately regulated by various extrinsic factors and intrinsic molecules, such as IL-6, IL-21, ICOS, Stat3, IRF4, and Batf. Because IL-21 receptor (IL-21R) is broadly expressed on T, B, NK, and dentritic cells (DCs), IL-21 signaling via Jak-Stat and other pathways has direct pleiotropic effects on their proliferation, differentiation, and effector function. For instance, while Th17 and TFH cells produce IL-21, IL-21 also facilitates the development of these cells. IL-21–producing TFH cells are important for the generation and maintenance of germinal centers, and control the differentiation of germinal center B cells and immunoglobulin production. Thus, IL-21R deficiency or IL-21 neutralization with IL-21R-Fc fusion protein prevents B cell-mediated autoimmunity in lupus-prone BXSB.B6-Yaa+ or MRL-Faslpr mouse models, respectively. IL-21 also enhances expansion and cytotoxicity of CD8+ effector T cells. During chronic lymphocytic choriomeningitis viral infection, chronic IL-21 production by antigen-specific CD4+ T cells is needed to sustain CD8+ T cell function for viral control. IL-21 is also required for the development of T cell-mediated type 1 diabetes in NOD mice, possibly through sustaining effector T cell function in a similar manner. Recently, two papers have shown that IL-21R-Fc prevents both auto- and allo-immune responses after islet transplantation. A timely discussion is thus needed to address the immune actions of IL-21 as well as the therapeutic potential of targeting IL-21 in transplantation.

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