Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model
Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model
复制标题
在小鼠系统性红斑狼疮模型中，IL-6 通过 Treg 抑制方法促进系统性红斑狼疮进展
DOI：
10.1007/s10067-014-2717-9
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Yin, Zhinan
中科院分区：
文献类型：
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作者：
Mao, Xiaoli;Wu, Yunyun;Yin, Zhinan
本研究旨在探讨白细胞介素6（IL-6）在系统性红斑狼疮（SLE）发病机制中的作用。用同基因激活的淋巴细胞衍生DNA（ALD-DNA）免疫正常雌性C57 BL/6小鼠，诱导SLE。未免疫的小鼠用作对照。SLE相关标志物，包括抗双链DNA（抗dsDNA）抗体，尿蛋白和肾脏组织病理学，进行了测定，以确保疾病的诱导。与对照组相比，ALD-DNA免疫组小鼠在体内外均表现出高水平的抗dsDNA抗体和IL-6表达。我们还发现，IL-6敲除（IL-6 KO）小鼠对ALD-DNA诱导的SLE具有抗性。免疫IL-6 KO小鼠的CD 4 +T细胞活化低于免疫野生型（Wt）小鼠。细胞内细胞因子染色结果显示，IL-6 KO免疫组Foxp 3表达高于Wt免疫组，这可能与疾病的严重程度有关。我们进一步发现ALD-DNA刺激的树突状细胞上清可导致IL-6和TNF-α的表达增加，并可抑制Foxp 3的表达。此外，阻断IL-6可上调Foxp 3的表达。因此，我们的研究结果表明，IL-6通过抑制Treg分化促进SLE的进展。
Our aim is to reveal the role of interleukin 6 (IL-6) in the pathogenesis of systemic lupus erythematosus (SLE) in a murine model of SLE. Normal female C57BL/6 mice were immunized with syngeneic-activated lymphocyte-derived DNA (ALD-DNA) to induce SLE. Non-immunized mice were used as control. SLE-associated markers, including anti-double-stranded DNA (anti-dsDNA) Abs, urine protein, and kidney histopathology, were assayed to ensure the induction of the disease. Compared with control mice, ALD-DNA immunized mice exhibited high levels of anti-dsDNA Abs, IL-6 expression in vivo and in vitro. We also found that IL-6 knockout (IL-6KO) mice were resistant to ALD-DNA-induced SLE. The activation of CD4+T cells in immunized IL-6KO mice was lower than in immunized wild-type (Wt) mice. Intracellular cytokine staining showed that Foxp3 expression in immunized IL-6KO mice was higher than in immunized Wt mice, which might be associated with the disease severity. We further discovered that ALD-DNA-stimulated dendritic cells supernatants could result in higher IL-6 and TNF-α expression and could suppress Foxp3 expression. In addition, blocking IL-6 could up-regulate Foxp3 expression. Therefore, our findings show that IL-6 promotes the progression of SLE via suppressing Treg differentiation.