Th 17-Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis 1
Th 17-Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis 1
复制标题
过敏性肺炎和肺纤维化小鼠模型中的 Th 17 极化免疫反应 1
DOI：
--
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Fabian Wehrmann
中科院分区：
文献类型：
--
作者：
R. O’Brien;A. Fontenot;Allison K. Lanham;F. D. D. Valle;W. Born;P. Simonian;C. Roark;Fabian Wehrmann
过敏性肺炎是一种以肺内弥漫性单个核细胞浸润为特征的环境肺部疾病，慢性暴露于吸入的银可进展为肺纤维化。使用已建立的过敏性肺炎小鼠模型，我们反复将C57BL/6小鼠暴露于直链糖多孢菌中，以研究肺纤维化是否需要T细胞。与野生型C57BL/6小鼠相比，在没有␣T细胞的情况下，TCR؊/؊小鼠暴露于直链球菌4wk后，肺内单核细胞浸润和胶原沉积明显减少。与CD_8؉T细胞相比，CD_4؉T细胞过继转移重建了新城疫杆菌诱导的炎症和纤维化反应，提示CD_4؉T细胞代表了关键的␣T细胞亚群。暴露于直链球菌后不同时间点的肺匀浆细胞因子分析未能确定主要的Th1或Th2表型。相反，IL-17在肺中的浓度随着持续暴露于直链球菌而增加。细胞内细胞因子染色显示，经直链球菌处理的小鼠肺组织中有14%的؉T细胞表达IL-17A。在没有IL-17受体信号的情况下，与野生型C57BL/6小鼠相比，Il17ra؊/؊小鼠的肺部炎症和纤维化显著减少。这些数据首次证明，在这种过敏性肺炎和肺纤维化的小鼠模型中，Th17极化的CD4؉T淋巴细胞在针对直链球菌属的免疫反应中发挥了重要作用。过敏性肺炎(Hp)3是一种因反复吸入雾化AGS(1)而引起的环境肺部疾病。病原体由多种有机颗粒(如哺乳动物和禽类蛋白、真菌和嗜热细菌)和某些小分子质量挥发性和非挥发性化合物组成。幽门螺杆菌的一个典型例子是法默肺病，它是由嗜热放线菌直链状糖多孢菌引起的。这种疾病发生在反复接触发霉干草的遗传易感人群中。幽门螺杆菌有几种临床形式(如急性、亚急性和慢性)，这取决于Ag的性质、暴露的数量和持续时间以及宿主/环境的相互作用(1)。这种急性形式的疾病通常是非进行性的，在停止接触银后会自动消失。亚急性和慢性疾病是由于持续低水平接触吸入的AGS造成的。在慢性亚组患者中，高达41%的患者出现肺纤维化，导致不可逆转的肺…
Hypersensitivity pneumonitis is an environmental lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. Using a well-established murine model of hypersensitivity pneumonitis, we repeatedly exposed C57BL/6 mice to Saccharopolyspora rectivirgula to investigate whether T cells are required for lung fibrosis. In the absence of ␣ T cells, TCR ؊/؊ mice exposed to S. rectivirgula for 4 wk had markedly decreased mononuclear infiltrates and collagen deposition in the lung compared with wild-type C57BL/6 mice. In contrast to CD8 ؉ T cells, adoptive transfer of CD4 ؉ T cells reconstituted the S. rectivirgula-induced inflammatory and fibrotic response, suggesting that the CD4 ؉ T cell represents the critical ␣ T cell subset. Cytokine analysis of lung homogenates at various time points after S. rectivirgula exposure failed to identify a predominant Th1 or Th2 phenotype. Conversely, IL-17 was found in the lung at increasing concentrations with continued exposure to S. rectivirgula. Intracellular cytokine staining revealed that 14% of CD4 ؉ T cells from the lung of mice treated with S. rectivirgula expressed IL-17A. In the absence of IL-17 receptor signaling, Il17ra ؊/؊ mice had significantly decreased lung inflammation and fibrosis compared with wild-type C57BL/6 mice. These data are the first to demonstrate an important role for Th17-polarized CD4 ؉ T lymphocytes in the immune response directed against S. rectivirgula in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis. H ypersensitivity pneumonitis (HP) 3 is an environmental lung disease that results from repeated inhalation of aerosolized Ags (1). The etiologic agents are composed of a wide variety of organic particles (e.g., mammalian and avian proteins, fungi, and thermophilic bacteria) and certain small molecular mass volatile and nonvolatile chemical compounds. A classic example of HP is Farmer's lung, which is caused by the thermophilic actinomycete Saccharopolyspora rectivirgula. This disorder occurs in genetically susceptible individuals who are repeatedly exposed to moldy hay. HP occurs in several clinical forms (e.g., acute, subacute, and chronic), depending on the nature of the Ag, the quantity and duration of exposure, and host/environment interactions (1). The acute form of disease is typically nonprogressive, with spontaneous resolution after cessation of Ag exposure. The subacute and chronic forms of disease result from continued low-level exposure to inhaled Ags. In the chronic subset of patients, pulmonary fibrosis occurs in up to 41% of cases, resulting in irreversible pulmonary …
登录
查看更多内容
影响因子：
32.4
作者：
Veldhoen, M;Hocking, RJ;Stockinger, B
通讯作者：
Stockinger, B
影响因子：
4.4
作者：
Gunnar Gudmundsson;M. Monick;G. Hunninghake
通讯作者：
Gunnar Gudmundsson;M. Monick;G. Hunninghake
DOI：
10.1165/ajrcmb.19.5.3153
发表时间：
1998-11-01
影响因子：
6.4
作者：
Gudmundsson, G;Bosch, A;Hunninghake, GW
通讯作者：
Hunninghake, GW
过敏性肺炎患者支气管肺泡灌洗 T 细胞的极化 1 型细胞因子谱。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yamasaki,H;Ando,M;Brazer,W;Center,DM;Cruikshank,WW
通讯作者：
Cruikshank,WW
影响因子：
9.6
作者：
Lukacs, NW;Hogaboam, C;Kunkel, SL
通讯作者：
Kunkel, SL