Tc17 cells are associated with cigarette smoke-induced lung inflammation and emphysema
Tc17 cells are associated with cigarette smoke-induced lung inflammation and emphysema
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DOI：
10.1111/resp.12486
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发表时间：
2015-04-01
期刊：
影响因子：
6.9
通讯作者：
Shen, Huahao
中科院分区：
文献类型：
--
作者：
Zhou, Hongbin;Hua, Wen;Shen, Huahao
背景与目的某些类型的T淋巴细胞，尤其是细胞毒性T细胞（Tc 1）和辅助性T细胞（Th 17）在吸烟所致的肺部疾病中起着关键作用。然而，Tc 17细胞是否参与其中仍然是未知的。我们调查了Tc 17参与使用香烟烟雾暴露model.Methodsgroups的小鼠暴露于香烟烟雾或过滤空气。分别于第2、8、12、24周处死小鼠，HE染色和/或免疫组化染色观察组织学变化。流式细胞仪检测肺、脾T细胞亚群的分布。此外，T细胞相关因子的表达水平进行了测量，通过实时聚合酶链反应或酶联免疫吸附试验。ResultsCigarette烟雾引起大量炎性细胞浸润，导致肺气肿。香烟烟雾暴露促进干扰素-γ（IFN）-和白细胞介素（IL）-17A在信使核糖核酸和蛋白质水平的表达。除了Tc 1和Th 17细胞外，肺和脾Tc 17细胞增加，这伴随着细胞因子IL-6、转化生长因子β（TGF-β）和转录因子Stat 3和RAR相关孤儿受体γ的上调。与未经处理的小鼠相比，H2 AX阳性细胞更频繁地观察到暴露于香烟烟雾中的小鼠。结论长期香烟烟雾暴露诱导的Tc 17细胞扩张的本地和远端，这是与肺气肿和脱氧核糖核酸损伤。作为IL-17 A的重要来源，该T细胞亚群可能是慢性阻塞性肺疾病治疗的潜在靶点。香烟烟雾暴露导致小鼠模型持续性炎症和肺气肿改变。香烟烟雾诱导局部和远端Tc 17（一种新型白细胞介素（IL）-17A产生细胞）扩增，这与脱氧核糖核酸（DNA）损伤有关。
Background and objectiveSome types of T lymphocytes, especially cytotoxic T-cells (Tc1) and T-helper (Th17) cells, play a pivotal role in cigarette smoke-induced lung diseases. However, whether Tc17 cells are involved remains largely unknown. We investigated Tc17 involvement using a cigarette smoke-exposure model.MethodsGroups of mice were exposed to cigarette smoke or filtered air. At weeks 2, 8, 12 and 24, mice were sacrificed to observe histological changes by HE stain and/or immunohistochemical staining. The frequency of T cell subsets in the lung and spleen were detected by flow cytometry. In addition, the expression levels of T cell-related factors were measured by real-time polymerase chain reaction or enzyme-linked immunosorbent assay.ResultsCigarette smoke caused substantial inflammatory cell infiltration and led to emphysema. Cigarette smoke exposure promoted the expression of interferon-gamma (IFN)- and interleukin (IL)-17A at the messenger ribonucleic acid and protein levels. In addition to Tc1 and Th17 cells, pulmonary and splenic Tc17 cells increased, which was accompanied by the upregulation of cytokines IL-6, transforming growth factor beta (TGF)-) and transcriptional factors Stat3 and RAR-related orphan receptor gamma. Compared with untreated mice, H2AX-positive cells were more frequently observed in mice exposed to cigarette smoke.ConclusionsLong-term cigarette smoke exposure induced Tc17 cell expansion both locally and distally, which was associated with emphysema and deoxyribonucleic acid damage. As an important source of IL-17A, this T cell subset may be a potential target for chronic obstructive pulmonary disease therapy.Cigarette smoke exposure led to persistent inflammation and emphysematous change in a mouse model. Cigarette smoke induced the expansion of Tc17, a novel type of interleukin (IL)-17A-producing cells, locally and distally, which was associated with deoxyribonucleic acid (DNA) damage.