Phenotypic alterations in type II alveolar epithelial cells in CD4+ T cell mediated lung inflammation.
Phenotypic alterations in type II alveolar epithelial cells in CD4+ T cell mediated lung inflammation.
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DOI：
10.1186/1465-9921-8-47
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发表时间：
2007-07-04
影响因子：
5.8
通讯作者：
Bruder D
中科院分区：
文献类型：
--
作者：
Gereke M;Gröbe L;Prettin S;Kasper M;Deppenmeier S;Gruber AD;Enelow RI;Buer J;Bruder D
尽管肺泡II型上皮细胞(AEC II)活动在呼吸系统免疫调节的各个方面的作用已得到越来越多的认识，但我们对AEC II转录体在免疫病理肺损伤中的作用仍知之甚少。我们以前已经建立了一个慢性T细胞介导的肺部炎症的小鼠模型，在该模型中，流感血凝素(HA)在AEC II中以转基因形式表达，在表达针对HA的II类限制性表位的转基因T细胞受体的小鼠中。这些小鼠的肺部炎症是由于CD4+T细胞对肺泡抗原的识别所致。这一模型被用来评估在CD4+T细胞介导的肺炎症中由抗原特异性识别触发的肺泡上皮靶细胞表达的炎症介质的分布。我们建立了一种允许流式细胞仪阴性选择和分离原代AEC II的方法，该方法具有高活性和高纯度。对从健康小鼠和急慢性CD4+T细胞介导的肺部炎症小鼠中分离的AEC II的mRNA进行全基因组转录图谱分析。T细胞介导的炎症与AEC II细胞表达多种细胞因子和趋化因子基因有关，提示上皮源性趋化因子在炎症细胞实质浸润中可能起重要作用。在形态上，活化的上皮细胞的大小增加，在分子水平上，炎症肺和正常肺的AEC II的比较转录组分析提供了在CD4+T细胞介导的肺炎背景下AEC II诱导的特异性炎症基因的详细特征。AEC II基因的表达在间质性肺炎的调控中起着重要作用，提示AEC II基因在肺间质性肺炎中的表达具有重要意义，这可能为研究肺炎性状态的分子发病机制提供依据。CD4+T细胞对AEC II细胞提呈的抗原的识别似乎是激活肺泡炎性转录体的有效触发因素。
Although the contribution of alveolar type II epithelial cell (AEC II) activities in various aspects of respiratory immune regulation has become increasingly appreciated, our understanding of the contribution of AEC II transcriptosome in immunopathologic lung injury remains poorly understood. We have previously established a mouse model for chronic T cell-mediated pulmonary inflammation in which influenza hemagglutinin (HA) is expressed as a transgene in AEC II, in mice expressing a transgenic T cell receptor specific for a class II-restricted epitope of HA. Pulmonary inflammation in these mice occurs as a result of CD4+ T cell recognition of alveolar antigen. This model was utilized to assess the profile of inflammatory mediators expressed by alveolar epithelial target cells triggered by antigen-specific recognition in CD4+ T cell-mediated lung inflammation. We established a method that allows the flow cytometric negative selection and isolation of primary AEC II of high viability and purity. Genome wide transcriptional profiling was performed on mRNA isolated from AEC II isolated from healthy mice and from mice with acute and chronic CD4+ T cell-mediated pulmonary inflammation. T cell-mediated inflammation was associated with expression of a broad array of cytokine and chemokine genes by AEC II cell, indicating a potential contribution of epithelial-derived chemoattractants to the inflammatory cell parenchymal infiltration. Morphologically, there was an increase in the size of activated epithelial cells, and on the molecular level, comparative transcriptome analyses of AEC II from inflamed versus normal lungs provide a detailed characterization of the specific inflammatory genes expressed in AEC II induced in the context of CD4+ T cell-mediated pneumonitis. An important contribution of AEC II gene expression to the orchestration and regulation of interstitial pneumonitis is suggested by the panoply of inflammatory genes expressed by this cell population, and this may provide insight into the molecular pathogenesis of pulmonary inflammatory states. CD4+ T cell recognition of antigen presented by AEC II cells appears to be a potent trigger for activation of the alveolar cell inflammatory transcriptosome.
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DOI：
10.1152/ajplung.1996.271.1.l54
发表时间：
1996-07-01
影响因子：
4.9
作者：
Buckley, S;Bui, KC;Warburton, D
通讯作者：
Warburton, D
影响因子：
15.3
作者：
Chvatchko, Y;KoscoVilbois, MH;Bonnefoy, JY
通讯作者：
Bonnefoy, JY
影响因子：
9.6
作者：
Cosio, MG;Majo, J;Cosio, MG
通讯作者：
Cosio, MG
DOI：
10.1152/ajplung.1996.270.3.l311
发表时间：
1996-03-01
影响因子：
4.9
作者：
Lesur, O;Arsalane, K;Lane, D
通讯作者：
Lane, D
影响因子：
4.4
作者：
Matzer, SP;Rödel, F;Beuscher, HU
通讯作者：
Beuscher, HU