Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus.
Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus.
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DOI：
10.1186/ar2964
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发表时间：
2010
影响因子：
4.9
通讯作者：
Kang I
中科院分区：
文献类型：
--
作者：
Shah K;Lee WW;Lee SH;Kim SH;Kang SW;Craft J;Kang I
白细胞介素(IL)-17是一种促炎细胞因子，主要由一种独特的CD4+ t辅助（Th）亚群Th17细胞产生。Th17细胞的发育受到Th1细胞产生的干扰素(IFN)-γ的抑制，提示Th17和Th1细胞之间存在交叉调节。因此，本研究分析了系统性红斑狼疮（SLE）患者和健康受试者外周血中CD4+ Th17和Th1细胞反应的平衡。招募了25名成年SLE患者和26名性别和年龄匹配（±2岁）的健康受试者。用肉豆蔻酸酯佛波酯（phorbol myristate acetate， PMA）和离子霉素刺激患者和健康人的外周血单个核细胞（PBMCs）体外4小时。流式细胞术检测CD4+ T细胞产生IL-17和/或IFN-γ的频率。评估CD4+ T细胞上th17相关趋化因子受体CCR4和CCR6的表达以及血浆中th17极化细胞因子的水平。疾病活动性通过SLE疾病活动性指数评分（SLEDAI）进行评估。采用非配对t检验和Pearson相关进行统计分析。与健康受试者相比，SLE患者CD4+IL-17+ T细胞的频率增加。然而，CD4+IFN-γ+ T细胞的频率在两组之间相似，表明SLE中Th17和Th1细胞反应的平衡发生了改变。SLE患者CD4+CCR4+CCR6+ T细胞（已知产生IL-17）的频率也增加。CD4+IL-17+ T细胞和CD4+CCR4+CCR6+ T细胞的频率与疾病活动性相关。在测量th17极化细胞因子的血浆水平时，SLE患者的IL-6水平高于健康受试者，尽管两组之间IL-1β、IL-21、IL-23和转化生长因子(TGF)-β的水平没有差异。我们证实Th17细胞反应增强与SLE患者的疾病活动性相关，提示IL-17在狼疮发病机制中的作用。我们的数据表明，参与平衡Th1和Th17调节以及产生IL-6的机制在SLE中是异常的，导致Th17反应增加。我们建议CD4+ T细胞上CCR4和CCR6的表达应被视为疾病活动性的标志物，IL-17阻断可能提供SLE的治疗靶点。
Interleukin (IL)-17 is a proinflammatory cytokine that is produced largely by a unique CD4+ T-helper (Th) subset called Th17 cells. The development of Th17 cells is suppressed by interferon (IFN)-γ produced by Th1 cells, suggesting cross-regulation between Th17 and Th1 cells. Thus, this study analyzed the balance of CD4+ Th17 and Th1 cell responses in peripheral blood from patients with systemic lupus erythematosus (SLE) and healthy subjects. Twenty-five adult patients with SLE and 26 healthy subjects matched for gender and age (± 2 years) were recruited. Peripheral blood mononuclear cells (PBMCs) from patients and healthy subjects were stimulated for 4 h ex vivo with phorbol myristate acetate (PMA) and ionomycin. The frequency of CD4+ T cells producing IL-17 and/or IFN-γ was measured by using flow cytometry. Expression of Th17-associated chemokine receptors CCR4 and CCR6 on CD4+ T cells as well as plasma levels of Th17-polarizing cytokines were assessed. Disease activity was evaluated by the SLE disease activity index score (SLEDAI). Unpaired t test and Pearson correlation were used for statistical analyses. Patients with SLE had an increased frequency of CD4+IL-17+ T cells compared with healthy subjects. However, the frequency of CD4+IFN-γ+ T cells was similar between the two groups, indicating an altered balance of Th17 and Th1 cell responses in SLE. Patients with SLE also had an increased frequency of CD4+CCR4+CCR6+ T cells that are known to produce IL-17. The frequency of CD4+IL-17+ T cells and CD4+CCR4+CCR6+ T cells correlated with disease activity. In measuring plasma levels of the Th17-polarizing cytokines, levels of IL-6 were higher in patients with SLE than in healthy subjects, although levels of IL-1β, IL-21, IL-23, and transforming growth factor (TGF)-β were not different between the two groups. We demonstrate an enhanced Th17 cell response that correlates with disease activity in patients with SLE, suggesting a role for IL-17 in the pathogenesis of lupus. Our data indicate that the mechanisms involved in balancing Th1 and Th17 regulation, as well as in producing IL-6, are aberrant in SLE, leading to an increased Th17 response. We suggest that CCR4 and CCR6 expression on CD4+ T cells should be considered as markers of disease activity, and that IL-17 blocking may offer a therapeutic target in SLE.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
14.2
作者：
Louten, Jennifer;Boniface, Katia;Malefyt, Rene de Waal
通讯作者：
Malefyt, Rene de Waal
影响因子：
5.5
作者：
Ortega, Consuelo;Fernandez-A, Silvia;Santamaria, Manuel
通讯作者：
Santamaria, Manuel