IL-25 promotes the function of CD4+CD25+T regulatory cells and prolongs skin-graft survival in murine models
IL-25 promotes the function of CD4+CD25+T regulatory cells and prolongs skin-graft survival in murine models
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IL-25 促进 CD4 CD25 T 调节细胞的功能并延长小鼠模型中皮肤移植物的存活
DOI：
10.1016/j.intimp.2015.03.036
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发表时间：
2015-10-01
影响因子：
5.6
通讯作者：
Liu, Zhongmin
中科院分区：
文献类型：
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作者：
Tang, Jiayou;Zhou, Xiaohui;Liu, Zhongmin
白细胞介素（IL）-25，也称为IL-17 E，属于细胞因子的IL-17家族。与其他IL-17家族成员不同，IL-25促进Th 2型免疫应答，刺激IL-4、IL-5和IL-13的产生。在这里，我们采用小鼠皮肤移植模型来探讨IL-25在抑制移植排斥反应中的作用。我们发现在同种异体移植排斥反应中IL-25表达增加，并且在IL-25 KO小鼠中同种异体移植排斥反应增强。IL-25 KO与CD 4 + T细胞中Foxp 3表达的下调相关。此外，虽然过继转移WT调节性T细胞（TCR 4）保护免于同种异体移植物排斥，过继转移IL-25缺陷型TCR 4未能保护免于同种异体移植物排斥。外源性IL-25在体外恢复Foxp 3表达和Treg功能。此外，IL-25促进NFAT 2的磷酸化。因此，IL-25可以通过上调NFAT 2磷酸化来增强Treg功能。我们的研究结果表明，IL-25可以维持Foxp 3的表达，增强TGFAP的抑制功能，并延长皮肤移植物的存活。(C)2015 Elsevier B. V.版权所有。
Interleukin (IL)-25, also known as IL-17E, belongs to the IL-17 family of cytokines. Unlike other IL-17 family members, IL-25 promotes Th2-type immune responses, stimulating IL-4, IL-5, and IL-13 production. Here, we employed murine models of skin graft to explore the role of IL-25 in suppression of graft rejection. We found that IL-25 expression is increased during allograft rejection, and allograft rejection was enhanced in IL-25 KO mice. IL-25 KO was associated with down-regulation of Foxp3 expression in CD4+ T cells. Further, while adoptive transfer of WT regulatory T cells (Tregs) protected against allograft rejection, adoptive transfer of IL-25 deficient Tregs failed to protect against allograft rejection. Exogenous IL-25 restored Foxp3 expression and Treg function in vitro. Moreover, IL-25 promoted phosphorylation of NFAT2. Thus, IL-25 may enhance Treg function by up-regulating NFAT2 phosphorylation. Our findings suggest that IL-25 can sustain Foxp3 expression, enhance the suppressive function of Tregs, and prolong skin-graft survival. (C) 2015 Elsevier B.V. All rights reserved.