Tregs promote the differentiation of Th17 cells in silica-induced lung fibrosis in mice.
Tregs promote the differentiation of Th17 cells in silica-induced lung fibrosis in mice.
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DOI：
10.1371/journal.pone.0037286
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Song L;Weng D;Liu F;Chen Y;Li C;Dong L;Tang W;Chen J
矽肺是一种因吸入矽尘而引起的职业性肺部疾病，以肺部炎症和纤维化为特征。以往的研究表明，TdR通过调节肺内免疫稳态的维持来调节矽肺的过程。Th 17细胞与Tcl 4有着共同的发育途径，通过募集和激活中性粒细胞在多种肺部疾病的免疫发病机制中发挥重要作用，但Tcl 4对SiO2诱导的肺纤维化中Th 17反应的调节作用尚待进一步研究。为探讨Th 17和IL-17在矽肺发生发展中的作用及其与Treg的相互作用，建立Treg缺失小鼠模型，并暴露于SiO2，建立SiO2诱导的肺纤维化实验模型。在这里，我们发现二氧化硅增加了肺纤维化中的Th 17反应。在二氧化硅诱导的肺纤维化中，凝血酶耗竭增强了中性粒细胞聚集并减弱了Th 17应答。mRNA和蛋白质表达结果均表明，TcR通过调节TGF-β1和IL-1β对Th 17细胞和IL-17具有调节作用。本研究提示，雷公藤多甙可通过调节TGF-β1和IL-1β促进矽肺小鼠肺纤维化中Th 17细胞的分化，这为进一步了解矽肺的发病过程及雷公藤多甙对Th 17细胞在肺部炎症中的调节机制提供了新的思路。
Silicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored. To evaluate the role of Th17 and IL-17 in the development of silicosis and their interaction with Tregs, Treg-depleted mice model was generated and exposed to silica to establish experimental model of silica-induced lung fibrosis. Here we showed that silica increased Th17 response in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein results showed that Tregs exerted its modulatory function on Th17 cells and IL-17 by regulating TGF-β1 and IL-1β. Our study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-β1 and IL-1β in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation.
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影响因子：
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