Zhou Hongbin, Hua Wen, Jin Yan, Zhang Chao, Che Luanqing, Xia Lixia, Zhou Jiesen, Chen Zhihua, Li Wen, Shen Huahao
Department of Respiratory and Critical Care Medicine, Second Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Respirology. 2015 Apr;20(3):426-33. doi: 10.1111/resp.12486. Epub 2015 Feb 11.
Some 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.
Groups 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.
Cigarette smoke caused substantial inflammatory cell infiltration and led to emphysema. Cigarette smoke exposure promoted the expression of interferon-gamma (IFN)-γ 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)-β) and transcriptional factors Stat3 and RAR-related orphan receptor gamma. Compared with untreated mice, γH2AX-positive cells were more frequently observed in mice exposed to cigarette smoke.
Long-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.
某些类型的T淋巴细胞，尤其是细胞毒性T细胞（Tc1）和辅助性T细胞（Th17），在香烟烟雾诱导的肺部疾病中起关键作用。然而，Tc17细胞是否参与其中仍 largely未知。我们使用香烟烟雾暴露模型研究了Tc17细胞的参与情况。
将小鼠分组暴露于香烟烟雾或过滤空气中。在第2、8、12和24周，处死小鼠，通过苏木精-伊红（HE）染色和/或免疫组织化学染色观察组织学变化。通过流式细胞术检测肺和脾中T细胞亚群的频率。此外，通过实时聚合酶链反应或酶联免疫吸附测定法测量T细胞相关因子的表达水平。
香烟烟雾导致大量炎性细胞浸润并导致肺气肿。香烟烟雾暴露促进了信使核糖核酸和蛋白质水平上干扰素-γ（IFN）-γ和白细胞介素（IL）-17A的表达。除了Tc1和Th17细胞外，肺和脾中的Tc17细胞增加，同时细胞因子IL-6、转化生长因子β（TGF）-β以及转录因子信号转导和转录激活因子3（Stat3）和视黄酸相关孤儿受体γ上调。与未处理的小鼠相比，在暴露于香烟烟雾的小鼠中更频繁地观察到γH2AX阳性细胞。
长期香烟烟雾暴露诱导局部和远处的Tc17细胞扩增，这与肺气肿和脱氧核糖核酸损伤有关。作为IL-17A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。
