Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis
Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis
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DOI：
10.1111/j.1365-2249.2009.04031.x
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发表时间：
2010-01-01
影响因子：
4.6
通讯作者：
Sumida, T.
中科院分区：
文献类型：
--
作者：
Wang, Y.;Ito, S.;Sumida, T.
为了确定狼疮性肾炎（LN）患者的细胞因子平衡，我们分析了肾脏浸润性T细胞。采用15例系统性红斑狼疮（SLE）患者的肾活检标本。根据国际肾脏病学会/肾脏病理学会的分类，将其分为III类、III+V类（III类为主组，n = 4）、IV类、IV+V类（IV类为主组，n = 7）和V类（n = 4）组。通过激光显微切割捕获肾小球和间质浸润细胞的单细胞样品。在III类为主、IV类为主和V类组中，肾小球和间质浸润性T细胞产生白细胞介素（IL）-2，IL-4，IL-10，IL-13和IL-17细胞因子。仅在III类主要和V类组样本的肾小球中检测到干扰素-γ。IL-17表达水平与血尿、血尿素氮、肾小球和肾小球疾病活动指数评分、肾小球尿蛋白、肾小球肌酐和肌酐清除率等临床指标密切相关。这表明肾小球浸润性T细胞可能充当辅助性T细胞1型（Th 1）、Th 2和Th 17细胞，而间质浸润性T细胞在III类为主和V类组中充当Th 2和Th 17细胞。与此相反，肾小球和间质浸润T细胞可能作为Th 2和Th 17细胞在IV类为主的组。细胞因子的平衡可能取决于肾脏病理的分类，IL-17可能在SLE的发展中发挥关键作用。
P>To determine the cytokine balance in patients with lupus nephritis (LN), we analysed kidney-infiltrating T cells. Renal biopsy samples from 15 systemic lupus erythematosus (SLE) patients were used. In accordance with the classification of International Society of Nephrology/Renal Pathology Society, they were categorized into Class III, Class III+V (Class III-predominant group, n = 4), Class IV, Class IV+V (Class IV-predominant group, n = 7) and Class V (n = 4) groups. The single-cell samples of both the glomelular and interstitial infiltrating cells were captured by laser-microdissection. The glomerular and interstitial infiltrating T cells produced interleukin (IL)-2, IL-4, IL-10, IL-13 and IL-17 cytokines in the Class III-predominant, Class IV-predominant and Class V groups. Interferon-gamma was detected only in the glomeruli of the Class III-predominant and Class V group samples. The expression level of IL-17 was correlated closely with clinical parameters such as haematuria, blood urea nitrogen level, SLE Disease Activity Index scores in both glomeruli and interstitium, urine protein level in glomeruli and serum creatinine and creatinine clearance levels in interstitium. This suggests that the glomerular infiltrating T cells might act as T helper type 1 (Th1), Th2 and Th17 cells while the interstitial infiltrating T cells, act as Th2 and Th17 cells in the Class III-predominant and Class V groups. In contrast, both the glomerular and interstitial infiltrating T cells might act as Th2 and Th17 cells in the Class IV-predominant group. The cytokine balances may be dependent upon the classification of renal pathology, and IL-17 might play a critical role in SLE development.