The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis
The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis
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DOI：
10.1177/0961203312457718
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发表时间：
2012-11-01
期刊：
影响因子：
2.6
通讯作者：
Lan, J-L
中科院分区：
文献类型：
--
作者：
Chen, D-Y;Chen, Y-M;Lan, J-L
辅助性T细胞17 （Th17）是一种新的T细胞亚群，可以分泌白细胞介素(IL)-17。虽然最近的数据表明Th17细胞和IL-17在狼疮肾炎（LN）的发病机制中起重要作用，但尚未对SLE患者肾脏中Th17相关细胞因子的表达进行详细研究。在本研究中，我们用流式细胞术研究了24例LN患者（17例IV级患者和7例V级患者）和12名健康对照者的循环th17细胞频率和血清th17相关细胞因子水平。我们还使用免疫组织化学方法研究了LN患者和最小变化肾病（MCN）患者肾小球中th17相关细胞因子的表达。我们的研究结果显示，LN患者循环Th17细胞的中位数频率（0.68%）显著高于健康对照组（0.12%,p < 0.001）。LN患者血清IL-17、IL-6和IL-23水平（中位数分别为7.26、232.60和37.01 pg/ml）显著高于健康对照组（中位数分别为0.82、34.60和7.42 pg/ml，均p < 0.001）。循环th17细胞频率与SLEDAI、肾SLEDAI、组织活性指数、细胞新月形程度、毛细血管内增殖呈正相关。与MCN患者和正常对照相比，IV级LN患者的肾活检中观察到肾小球IL-17和IL-23表达水平显著升高。肾小球IL-17和IL-23表达水平与LN患者肾SLEDAI和组织学活动指数呈正相关。我们的研究结果提示IL-23/Th17轴在SLE肾内炎症中的潜在作用。狼疮杂志，2012,21,1385-1396。
T helper type 17 (Th17) cells, a novel distinct subset of Th cell, can secrete interleukin (IL)-17 in humans. Although recent data suggest that Th17 cells and IL-17 play an important role in the pathogenesis of lupus nephritis (LN), the expression of Th17-related cytokines in the kidneys of SLE patients has not been studied in detail. In the present study, we investigated circulating Th17-cell frequencies using flow cytometry and serum Th17-related cytokine levels by enzyme-linked immunosorbent assay (ELISA) in 24 LN patients (17 patients with class IV and seven patients with class V) and 12 healthy controls. We also investigated glomerular Th17-related cytokine expression in LN patients and minimal change nephropathy (MCN) patients using immunohistochemistry. Our results showed significantly higher median frequencies of circulating Th17 cells in LN patients (0.68%) than in healthy controls (0.12%, p < 0.001). Serum levels of IL-17, IL-6 and IL-23 were significantly higher in LN patients (median 7.26, 232.60 and 37.01 pg/ml, respectively) than in healthy controls (median 0.82, 34.60 and 7.42 pg/ml, respectively; all p < 0.001). Circulating Th17-cell frequencies were positively correlated with SLEDAI, renal SLEDAI and histological activity index, the degree of cellular crescent and endocapillary proliferation. Significantly higher levels of glomerular IL-17 and IL-23 expression were observed in renal biopsies from class IV LN patients as compared to those from MCN patients and normal controls. Glomerular IL-17 and IL-23 expression levels were positively correlated with renal SLEDAI and histological activity index for LN patients. Our results suggest the potential role of the IL-23/Th17 axis in the intra-renal inflammation of SLE. Lupus (2012) 21, 1385-1396.