Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.
Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.
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患有慢性同种异体功能障碍的肾脏移植受者中Th17细胞表型的增加。
DOI：
10.1371/journal.pone.0145258
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yang CW
中科院分区：
文献类型：
--
作者：
Chung BH;Kim KW;Kim BM;Doh KC;Cho ML;Yang CW
本研究旨在确定Th 17细胞表型与肾移植受者（KTR）慢性移植物功能障碍的相关性。我们比较了慢性移植物功能障碍组（CAD，n = 52）与四个对照组（长期稳定KTR（LTS，n = 67）、早期稳定KTR（ES，n = 28）、终末期肾病（ESRD，n = 45）和健康对照（HC，n = 26））中Th 17细胞表型的表达。我们还使用人近端肾小管上皮细胞系（HPRTEpiC）进行体外研究以评估IL-17对人肾小管上皮细胞的作用。与LTS组和其他对照组相比，CAD组显示出CD 4 + T细胞中Th 17细胞的百分比增加，并且效应记忆T细胞或CCR 4 + CCR 6 +/CD 4 + T细胞中IL-17产生细胞的比例也增加。此外，与LTS组相比，CAD组的IL-17、IL-33和IL-1 β的血清水平以及IL-1 β、IL-33和HMGB 1 mRNA的表达均升高。体外研究显示，IL-17以剂量依赖性方式增加HPRTEpiC中IL-6和IL-8的产生，并上调促纤维化基因如ACTA-2和CTGF的表达，这表明IL-17在肾小管细胞损伤的发展中具有作用。我们的研究结果可能表明，Th 17细胞表型的增加可能是慢性同种异体移植物损伤的标志物，因此需要开发针对Th 17细胞通路的诊断和治疗工具。
This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.