CCL20 secreted from IgA1-stimulated human mesangial cells recruits inflammatory Th17 cells in IgA nephropathy.
CCL20 secreted from IgA1-stimulated human mesangial cells recruits inflammatory Th17 cells in IgA nephropathy.
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IgA1刺激的人系膜细胞分泌的CCL20在IgA肾病中招募炎症性Th17细胞
DOI：
10.1371/journal.pone.0178352
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Lu G;Zhang X;Shen L;Qiao Q;Li Y;Sun J;Zhang J
IgA肾病（IgAN）是最常见的原发性肾小球肾炎，其特征是人系膜细胞（HMC）增殖和细胞外基质扩张，与由半乳糖缺乏的IgA1组成的免疫沉积有关。然而，IgA1对IgAN的作用机制尚未完全阐明。在本研究中，iga1处理的HMC中趋化因子的表达谱比对照组发生了更大的变化。CCL20在IgAN患者或iga1治疗的HMC患者血清中均显著升高。进一步的实验表明，CCL20的唯一受体CCR6在活化的T细胞中高表达。细胞内染色和细胞因子表达谱表明CCR6+ T细胞产生高水平的IL-17。Transwell实验、免疫组化和免疫荧光实验广泛证实CCL20可将炎性Th17细胞募集到肾脏。这些现象引起一系列免疫炎症反应，进一步损害肾脏。因此，受IgA1刺激的HMC可以产生CCL20，从而将炎症性Th17细胞募集到肾脏，诱导IgA肾病进一步病变。
IgA nephropathy (IgAN) is the most common primary glomerulonephritis characterized by human mesangial cells (HMC) proliferation and extracellular matrix expansion associated with immune deposits consisting of galactose-deficient IgA1. However, how IgA1 contributes to IgAN has yet to be completely elucidated. In this study, the expression profile of chemokines was more altered in IgA1-treated HMC than in the control group. CCL20 was significantly higher either in the serum of IgAN patients or in IgA1-treated HMC. Further experiments demonstrated that CCR6, the only receptor of CCL20, was highly expressed in activated T cells. Intracellular staining assay and cytokine expression profile implied that CCR6+ T cells produced high IL-17 levels. Transwell experiment immunohistochemistry and immunofluorescence experiments extensively demonstrated that CCL20 could recruit inflammatory Th17 cells to the kidneys. These phenomena caused a series of immune inflammatory responses and further damaged the kidneys. Therefore, HMC stimulated by IgA1 could produce CCL20 and consequently recruit inflammatory Th17 cells to the kidneys to induce further lesion in IgA nephropathy.