IL-17 promotes Type 1 T cell response through modulating dendritic cell function in acute allograft rejection.
IL-17 promotes Type 1 T cell response through modulating dendritic cell function in acute allograft rejection.
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DOI：
10.1016/j.intimp.2014.03.010
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发表时间：
2014-06
影响因子：
5.6
通讯作者：
L. Duan;Jie Chen;Quansong Xia;Liying Chen;Kai Fan;K. Sigdel;M. Fang;F. Zheng;Guixiu Shi;F. Gong
中科院分区：
文献类型：
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作者：
L. Duan;Jie Chen;Quansong Xia;Liying Chen;Kai Fan;K. Sigdel;M. Fang;F. Zheng;Guixiu Shi;F. Gong
IL-17是由多种细胞产生的细胞因子。先前的研究已经表明，IL-17在不同疾病的发病机制中起着关键作用。然而，很少有研究涉及IL-17在同种异体移植排斥反应发生中的来源和机制。在这项研究中，我们提出，IL-17的表达在心脏移植排斥反应的早期阶段达到最强的反应，并在DC成熟之前升高。IL-17主要由CD 3 +T细胞产生，而CD 11 c、CD 11b和NK1.1阳性细胞很少表达IL-17。值得注意的是，阻断内源性IL-17活性抑制DC成熟，减少炎性细胞因子和受损的Th 1免疫反应在急性同种异体排斥反应。此外，从IL-17处理的小鼠过继转移DC具有显著更长的同种异体移植物存活时间和由T细胞产生的IFN-γ的数量减少。因此，在体外实验中，重组IL-17显著上调骨髓来源的树突状细胞（BMDCs）的共刺激分子，并且IL-17处理的BMDCs显示增强T细胞功能的能力增加。总之，我们的数据提供了明确的证据表明，早期升高的IL-17水平有助于通过调节树突状细胞功能的同种异体移植排斥反应。
IL-17 is a cytokine that produced by various type of cell. Previous studies have been shown that IL-17 plays a critical role in the pathogenesis of different diseases. However, few studies have addressed the source and mechanism of IL-17 in the development of allograft rejection response. In this study, we present that the IL-17 expression reaches the strongest response at the early stage of cardiac allograft rejection, and was elevated earlier than DC maturation. The IL-17 is predominantly produced by CD3+T cells, whereas CD11c, CD11b, and NK1.1 positive cells rarely expressed IL-17. It is worth noting that blockade of endogenous IL-17 activity suppressed DC maturation, decreased inflammatory cytokines and impaired Th1 immune response during acute allograft rejection. Furthermore, adoptive transfer with DCs from IL-17-treated mice had a significant longer allograft survival time and decreased number of IFN-γ produced by T cells. Consistently, in an in vitro experiment, recombinant IL-17 significantly up-regulate co-stimulatory molecules of bone marrow derived dendritic cells (BMDCs), and IL-17-treated BMDCs show that an increased capacity to enhance T cell function was also observed. In conclusion, our data provide clear evidence that the early elevated level of IL-17 contributes to allograft rejection through modulating dendritic cell function.