A pathogenic role of IL-17 at the early stage of corneal allograft rejection
A pathogenic role of IL-17 at the early stage of corneal allograft rejection
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DOI：
10.1016/j.trim.2009.03.006
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发表时间：
2009-07-01
影响因子：
1.5
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
--
作者：
Chen, Haiyong;Wang, Weilin;Zheng, Shusen
目的：Th 17细胞是新近发现的一种新的效应性Th细胞亚群，参与微生物感染和自身免疫。然而，这些细胞在器官移植排斥反应中的作用在很大程度上仍然未知。在这项研究中，我们调查是否Th 17细胞参与同种异体角膜排斥反应在mouse model.Methods：供体角膜（C57 BL/6）移植到原位移植床Balb/c受体。在角膜移植术后不同时间点，分别用流式细胞术和定量RT-PCR检测引流颈淋巴结（LN）和移植角膜中Th 17和Th 1相关细胞因子的表达。此外。使用IL-17-/-Balb/c小鼠来确定Th 17细胞对同种异体角膜存活的影响。最后，在IL-17-/-受体移植后的Th 1和促炎细胞因子的配置文件进行了examined.Results：Th 17的表达显着增强，在炎症移植和引流淋巴结在早期阶段的同种异体角膜排斥反应，而上调的Th 1产生IFN-γ被认为是在后期。在同种异体辅助细胞激活后，与对照相比，来自移植受体的引流LN中的应答细胞分泌高水平的IL-6、TGF-β和IL-21，这可能驱动幼稚T细胞分化为Th 17细胞。重要的是，IL-17缺乏导致同种异体排斥反应的延迟发展，但不影响移植物的总体存活时间。结论：Th 17细胞在角膜移植排斥反应的早期起着促炎作用。(C)2009爱思唯尔有限公司版权所有。
Purpose: Th17, recently identified as a new subset of effector Th cells, has been shown to be involved in microbe infection and autoimmunity. However, the role of these cells in organ allograft rejection remains largely unknown. In this study, we investigate whether Th17 cells participate in allogeneic corneal rejection in a mouse model.Methods: Donor cornea (C57BL/6) was transplanted into orthotopic graft bed of Balb/c recipients. At different time points after keratoplasty, the expression of Th17 and Th1-related cytokines in draining cervical lymph nodes (LN) and grafted cornea was examined by flow cytometry and quantitative RT-PCR, respectively. Furthermore. IL-17-/-Balb/c mice were used to determine the effects of Th17 cells on allogeneic cornea survival. Finally, the profiles of Th1 and proinflammatory cytokines in IL-17-/- recipients after transplantation were examined.Results: Th17 expression was enhanced significantly in inflamed transplants and draining lymph nodes at the early stage of allocorneal rejection, while upregulation of Th1 producing IFN-gamma was seen in the late phase. Upon activation by allogeneic accessory cells, responder cells in draining LN from transplanted recipients secreted high levels of IL-6, TGF-beta and IL-21 compared to controls, which may drive naive T cells to differentiate into Th17 cells. Importantly, IL-17 deficiency led to the delayed development of allogeneic rejection, but did not affect the overall survival time of transplants. This effect correlated with restrained Th1 polarization and decreased production of proinflammatory cytokines.Conclusion: Th17 cells play a disease-promoting role at the early stage of corneal allograft rejection. (C) 2009 Elsevier B.V. All rights reserved.