Duan Lihua, Chen Jie, Xia Quansong, Chen Liying, Fan Kai, Sigdel K R, Fang Min, Zheng Fang, Shi Guixiu, Gong Feili
Department of Rheumatology and Clinical Immunology, The First Hospital of Xiamen University, Xiamen, China.
Basic Medical Department of Medical College, Xiamen University, Xiamen, China.
Int Immunopharmacol. 2014 Jun;20(2):290-7. doi: 10.1016/j.intimp.2014.03.010. Epub 2014 Mar 25.
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.
白细胞介素-17（IL-17）是一种由多种类型细胞产生的细胞因子。先前的研究表明，IL-17在不同疾病的发病机制中起关键作用。然而，关于IL-17在同种异体移植排斥反应发生过程中的来源和机制的研究很少。在本研究中，我们发现IL-17的表达在心脏同种异体移植排斥反应的早期达到最强反应，并且比树突状细胞（DC）成熟更早升高。IL-17主要由CD3(+) T细胞产生，而CD11c、CD11b和NK1.1阳性细胞很少表达IL-17。值得注意的是，在急性同种异体移植排斥反应期间，阻断内源性IL-17活性可抑制DC成熟，减少炎性细胞因子并损害Th1免疫反应。此外，移植来自经IL-17处理小鼠的DC可显著延长同种异体移植存活时间，并减少T细胞产生的干扰素-γ数量。同样，在体外实验中，重组IL-17可显著上调骨髓来源树突状细胞（BMDC）的共刺激分子，并且经IL-17处理的BMDC也显示出增强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，即早期升高的IL-17水平通过调节树突状细胞功能促进同种异体移植排斥反应。
