Infiltration of IL-17-Producing T Cells and Treg Cells in a Mouse Model of Smoke-Induced Emphysema
Infiltration of IL-17-Producing T Cells and Treg Cells in a Mouse Model of Smoke-Induced Emphysema
复制标题
烟雾诱发肺气肿小鼠模型中产生 IL-17 的 T 细胞和 Treg 细胞的浸润
DOI：
10.1007/s10753-016-0365-8
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发表时间：
2016-08-01
期刊：
影响因子：
5.1
通讯作者：
Liang, Yi
中科院分区：
文献类型：
--
作者：
Duan, Min-Chao;Zhang, Jian-Quan;Liang, Yi
慢性阻塞性肺疾病（COPD）是一种与活化T细胞积累相关的进行性和不可逆的慢性炎症性疾病。迄今为止，关于Th17、Tc17和调节性T （Treg）细胞在COPD中的内在关联的信息很少。本研究旨在探讨香烟致肺气肿小鼠肺CD4(+)Foxp3(+) Treg细胞和产生il -17的CD4和CD8 （Th17和Tc17）淋巴细胞的变化。几组老鼠暴露在香烟烟雾或室内空气中。12周、24周处死小鼠，HE染色观察组织学变化。流式细胞术检测各组小鼠肺组织中Th17 (CD4（+)IL-17(+)T）、Tc17 (CD8（+)IL-17(+)T）、Treg (CD4（+)Foxp3(+)T）细胞的频率。实时定量聚合酶链反应检测孤儿核受体ROR γ t和Foxp3 mRNA水平。采用酶联免疫吸附法检测小鼠白细胞介素-17 （IL-17）、IL-6、IL-10和转化生长因子- β (tgf - β 1)蛋白水平。香烟烟雾引起空气空间的大量扩大，并伴有正常肺泡结构的破坏，导致肺气肿。Th17和Tc17细胞的频率，以及IL-6、IL-17、tgf - β 1和ROR γ t的表达在香烟烟雾（CS）暴露小鼠的肺部更高，特别是在24周的CS暴露小鼠中。cs暴露小鼠Treg细胞频率、IL-10、Foxp3表达均低于对照组。更重要的是，Tregs的频率与Th17细胞和Tc17细胞呈负相关。有趣的是，浸润肺部的细胞中有很大一部分倾向于Tc17表型。我们的研究结果提示Th17、Tc17和Treg细胞在COPD发病机制中的作用。这些细胞的再平衡将有助于开发和完善COPD的新免疫疗法。
Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease associated with the accumulation of activated T cells. To date, there is little information concerning the intrinsic association among Th17, Tc17, and regulatory T (Treg) cells in COPD. The objective of this study was to investigate the variation of lungs CD4(+)Foxp3(+) Treg cells and IL-17-producing CD4 and CD8 (Th17 and Tc17) lymphocytes in mice with cigarette-induced emphysema. Groups of mice were exposed to cigarette smoke or room air. At weeks 12 and 24, mice were sacrificed to observe histological changes by HE stain. The frequencies of Th17 (CD4(+)IL-17(+)T), Tc17 (CD8(+)IL-17(+)T), and Treg (CD4(+)Foxp3(+)T) cells in lungs from these mice were analyzed by flow cytometry. The mRNA levels of orphan nuclear receptor ROR gamma t and Foxp3 were performed by real-time quantitative polymerase chain reaction. The protein levels of interleukin-17 (IL-17), IL-6, IL-10, and transforming growth factor-beta (TGF-beta 1) were measured by enzyme-linked immunosorbent assay. Cigarette smoke caused substantial enlargement of the air spaces accompanied by the destruction of the normal alveolar architecture and led to emphysema. The frequencies of Th17 and Tc17 cells, as well as the expressions of IL-6, IL-17, TGF-beta 1, and ROR gamma t were greater in the lungs of cigarette smoke (CS)-exposed mice, particularly in the 24-week CS-exposed mice. The frequencies of Treg cells and the expressions of IL-10 and Foxp3 were lower in CS-exposed mice compared to control group. More important, the frequencies of Tregs were negatively correlated with Th17 cells and with Tc17 cells. Interestingly, a significant portion of the cells that infiltrate the lungs was skewed towards a Tc17 phenotype. Our findings suggest the contribution of Th17, Tc17, and Treg cells in the pathogenesis of COPD. Rebalance of these cells will be helpful for developing and refining the new immunological therapies for COPD.