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Infiltration of IL-17-Producing T Cells and Treg Cells in a Mouse Model of Smoke-Induced Emphysema

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Abstract

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 γt 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-β1) 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-β1, and ROR γt 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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China Grant 81360011 and 81460009, by Guangxi Natural Science Foundation of China Grant 2013GXNSFAA019256, and by Nanning Science and Technology Program, China (No. 20143161 and No.20153088).

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Authors and Affiliations

  1. Department of Respiratory Medicine, The Eighth People’s Hospital of Nanning, Nanning, Guangxi, 530001, China

    Min-Chao Duan, Yue Liang & Jin Xiao

  2. Department of Respiratory Medicine, The First Afiltrated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China

    Min-Chao Duan, Jian-Quan Zhang, Guang-Nan Liu, Hai-Juan Tang & Yi Liang

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  1. Min-Chao Duan
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  2. Jian-Quan Zhang
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Correspondence to Jian-Quan Zhang.

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All experimental protocols were approved by the Ethical Committee for Animal Research of Guangxi Medical University.

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Duan, MC., Zhang, JQ., Liang, Y. et al. Infiltration of IL-17-Producing T Cells and Treg Cells in a Mouse Model of Smoke-Induced Emphysema. Inflammation 39, 1334–1344 (2016). https://doi.org/10.1007/s10753-016-0365-8

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