The Th17 pathway in the peripheral lung microenvironment interacts with expression of collagen V in the late state of experimental pulmonary fibrosis
The Th17 pathway in the peripheral lung microenvironment interacts with expression of collagen V in the late state of experimental pulmonary fibrosis
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DOI：
10.1016/j.imbio.2014.08.011
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发表时间：
2015-01-01
期刊：
影响因子：
2.8
通讯作者：
Capelozzi, Vera L.
中科院分区：
文献类型：
--
作者：
Fabro, Alexandre T.;da Silva, Pedro H. R. Q.;Capelozzi, Vera L.
背景资料：在肺纤维化的发病机制中，来源于成纤维细胞的肌成纤维细胞引起基质蛋白（包括胶原V）的过度和无序沉积，这可引起Th 17介导的免疫应答并导致细胞凋亡。然而，肺纤维化细胞产生基质的内在能力是否取决于其位点特异性的变异尚不清楚。目的：研究实验性肺纤维化后期外周肺微环境中维持肺重构的Th 17和胶原V之间的联系。在用博来霉素处理后21天处死年轻雄性小鼠，包括野生Balb/c小鼠（BALB，n = 10）、野生C57 Black/6 J小鼠（C57，n = 10）和IL-17受体A敲除小鼠（KO，n = 8）。采用天狼星红染色、IL-17相关标志物的免疫组织化学和细胞凋亡的“原位”检测、I型和V型胶原的免疫荧光、用于RT-PCR和电子显微镜的来自组织肺外植体的原代细胞培养物。与Balb小鼠相比，C57小鼠在晚期阶段肌成纤维细胞的细胞外基质成分的外周沉积得以维持，并且在C57小鼠中没有改变。IL-17受体A的缺失可诱导V型胶原的过度表达，增强IL-17及其相关细胞因子的外周表达，减少外周肺成纤维细胞凋亡。结论：胶原V和IL-17表达模式之间的正反馈环可能在缺乏IL-17的情况下协调外周胶原I的维持。17受体A在纤维化易感菌株中以位点特异性方式。(C)2014 Elsevier GmbH. All rights reserved.
Background: Myofibroblasts derived from fibroblasts in the pathogenesis of pulmonary fibrosis causes excessive and disordered deposition of matrix proteins, including collagen V, which can cause a Th17-mediated immune response and lead to apoptosis. However, whether the intrinsic ability of lung FBs to produce the matrix depends on their site-specific variations is not known.Aim: To investigate the link between Th17 and collagen V that maintains pulmonary remodeling in the peripheral lung microenvironment during the late stage of experimental pulmonary fibrosis.Methods: Young male mice including wild Balb/c mice (BALB, n = 10), wild C57 Black/6J mice (C57, n = 10) and IL-17 receptor A knockout mice (KO, n = 8), were sacrificed 21 days after treatment with bleomycin. Picrosirius red staining, immunohistochemistry for IL-17-related markers and "in situ" detection of apoptosis, immunofluorescence for collagen types I and V, primary cell cultures from tissue lung explants for RT-PCR and electron microscopy were used.Results: The peripheral deposition of extracellular matrix components by myofibroblasts during the late stage is maintained in C57 mice compared with that in Balb mice and is not changed in the absence of IL-17 receptor A; however, the absence of IL-17 receptor A induces overexpression of type V collagen, amplifies the peripheral expression of IL-17 and IL-17-related cytokines and reduces peripheral lung fibroblast apoptosis.Conclusion: A positive feedback loop between the expression patterns of collagen V and IL-17 may coordinate the maintenance of peripheral collagen I in the absence of IL-17 receptor A in fibrosis-susceptible strains in a site-specific manner. (C) 2014 Elsevier GmbH. All rights reserved.