CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of silica-induced lung fibrosis in mice.
CD4+CD25+Foxp3+ regulatory T cells depletion may attenuate the development of silica-induced lung fibrosis in mice.
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DOI：
10.1371/journal.pone.0015404
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发表时间：
2010-11-03
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：
Liu F;Liu J;Weng D;Chen Y;Song L;He Q;Chen J
矽肺是一种因吸入二氧化硅粉尘而引起的以肺部炎症和纤维化为特征的职业性肺部疾病。以往的研究表明，Th1和Th2细胞因子参与了矽肺的发病过程，但Th1/Th2极化在矽肺发生发展过程中的作用仍存在争议。调节性T细胞(Treg细胞)通过调节Th1/Th2极化在调节免疫动态平衡中发挥重要作用，但它们在矽肺中的可能意义仍有待探讨。为探讨Treg细胞在矽肺发生发展中的作用，我们用抗CD25单抗建立Treg耗竭小鼠模型，并通过气管内注入二氧化硅建立实验性矽肺纤维化模型。病理检查显示，Treg耗竭小鼠早期易发生更严重的炎症反应，炎性细胞浸润增强。此外，Treg细胞的耗尽会延缓二氧化硅诱导的小鼠肺纤维化的进展。进一步研究细胞因子的mRNA表达显示，Tregs的耗竭导致Th1细胞因子的产生增加，Th2细胞因子的产生减少。流式细胞术和实时定量聚合酶链式反应研究表明，在矽肺纤维化过程中，Treg细胞在炎症阶段直接通过表达CTLA-4发挥调节作用，在纤维化阶段通过增加IL-10和转化生长因子-β的分泌而间接发挥调节作用。我们的研究表明，在二氧化硅诱导的肺纤维化中，Tregs的耗竭可能延缓了二氧化硅诱导的肺纤维化的进展，并增强了Th1反应，减缓了Th1/Th2平衡向Th2表型转变。在矽肺炎症阶段，Treg细胞的调节作用可能依赖于直接机制和间接机制。
Silicosis is an occupational lung disease caused by inhalation of silica dust characterized by lung inflammation and fibrosis. Previous study showed that Th1 and Th2 cytokines are involved in silicosis, but Th1/Th2 polarization during the development of silicosis is still a matter of debate. Regulatory T cells (Treg cells) represent a crucial role in modulation of immune homeostasis by regulating Th1/Th2 polarization, but their possible implication in silicosis remains to be explored. To evaluate the implication of Treg cells in the development of silicosis, we generated the Treg-depleted mice model by administration of anti-CD25 mAbs and mice were exposed to silica by intratracheal instillation to establish experimental model of silica-induced lung fibrosis. The pathologic examinations show that the Treg-depleted mice are susceptive to severer inflammation in the early stage, with enhanced infiltration of inflammatory cells. Also, depletion of Treg cells causes a delay of the progress of silica-induced lung fibrosis in mice model. Further study of mRNA expression of cytokines reveals that depletion of Tregs leads to the increased production of Th1-cytokines and decreased production of Th2-cytokine. The Flow Cytometry and realtime PCR study show that Treg cells exert the modulation function both directly by expressing CTLA-4 at the inflammatory stage, and indirectly by secreting increasing amount of IL-10 and TGF-β during the fibrotic stage in silica-induced lung fibrosis. Our study suggests that depletion of Tregs may attenuate the progress of silica-induced lung fibrosis and enhance Th1 response and decelerate Th1/Th2 balance toward a Th2 phenotype in silica-induced lung fibrosis. The regulatory function of Treg cells may depend on direct mechanism and indirect mechanism during the inflammatory stage of silicosis.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.2
作者：
Bellinghausen, I;Klostermann, B;Saloga, J
通讯作者：
Saloga, J
DOI：
10.1165/ajrcmb.24.4.4249
发表时间：
2001-04-01
影响因子：
6.4
作者：
Arras, M;Huaux, F;Lison, D
通讯作者：
Lison, D
影响因子：
4.4
作者：
Haeryfar, SMM;DiPaolo, RJ;Yewdell, JW
通讯作者：
Yewdell, JW