The Emerging Role of Interleukin-21 in Transplantation.
The Emerging Role of Interleukin-21 in Transplantation.
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DOI：
10.4172/2155-9899.s9-002
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发表时间：
2012-08-24
期刊：
影响因子：
--
通讯作者：
Chen W
中科院分区：
文献类型：
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作者：
Xie A;Buras ED;Xia J;Chen W
自2000年发现以来，IL-21已被证明在先天性和适应性免疫应答的调节中发挥关键作用。IL-21主要由多种效应CD 4 + T细胞类型[辅助性T细胞17（Th 17）、滤泡辅助性T细胞（TFH）和其他活化的CD 4+细胞]和NKT细胞产生。除了T细胞受体（TCR）信号外，活化的CD 4 + T细胞产生IL-21还受到各种外在因子和内在分子的复杂调节，如IL-6、IL-21、ICOS、Stat 3、IRF 4和Batf。由于IL-21受体（IL-21 R）在T、B、NK和树突状细胞（DC）上广泛表达，通过Jak-Stat和其他途径的IL-21信号传导对它们的增殖、分化和效应器功能具有直接多效性作用。例如，虽然Th 17和TFH细胞产生IL-21，但IL-21也促进这些细胞的发育。产生IL-21的TFH细胞对于生殖中心的产生和维持是重要的，并且控制生殖中心B细胞的分化和免疫球蛋白的产生。因此，IL-21 R缺陷或IL-21与IL-21 R-Fc融合蛋白的中和分别在狼疮易感BXSB. B6-Yaa+或MRL-Faslpr小鼠模型中阻止了B细胞介导的自身免疫。IL-21还增强CD 8+效应T细胞的扩增和细胞毒性。在慢性淋巴细胞性脉络丛脑膜炎病毒感染期间，需要抗原特异性CD 4 + T细胞的慢性IL-21产生来维持CD 8 + T细胞功能以控制病毒。IL-21也是NOD小鼠中T细胞介导的1型糖尿病的发展所必需的，可能是通过以类似的方式维持效应T细胞功能。最近，有两篇论文表明，IL-21 R-Fc可预防胰岛移植后的自体和同种异体免疫反应。因此，需要及时讨论IL-21的免疫作用以及靶向IL-21在移植中的治疗潜力。
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.