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Inflammation Research

, Volume 68, Issue 11, pp 957–968 | Cite as

Rapamycin attenuates Tc1 and Tc17 cell responses in cigarette smoke-induced emphysema in mice

  • Hui Zhang
  • Xiu Zhou
  • Xin Chen
  • Yuanzhen Lin
  • Shilin Qiu
  • Yun Zhao
  • Qiya Tang
  • Yi Liang
  • Xiaoning ZhongEmail author
Original Research Paper
  • 102 Downloads

Abstract

Objective and design

Chronic exposure to cigarette smoke promotes airway inflammation and emphysema accompanied by enhanced CD8+ interferon (IFN)-γ+ T(Tc1) and CD8+ interleukin (IL)-17+ T(Tc17) cell responses. The mammalian target of rapamycin (mTOR) has been involved in the pathogenesis of emphysema. Inhibiting mTOR by rapamycin has been reported to alleviate emphysema, but the mechanism is not fully understood. We aimed to explore the effect of rapamycin on Tc1 and Tc17 cell responses induced by cigarette smoke exposure.

Materials

Male C57BL/6 mice were exposed to cigarette smoke or room air for 24 weeks. Half of the smoke-exposed mice received rapamycin in the last 12 weeks. The severity of emphysema in those mice was evaluated by mean linear intercept (MLI), mean alveolar airspace area (MAA) and destructive index (DI). Bronchoalveolar lavage was collected and analyzed. Phosphorylated (p-) mTOR in CD8+ T cells, Tc1 and Tc17 cells were detected by flow cytometry. The relative expression of p-mTOR in lungs was determined by western blot analysis. IFN-γ and IL-17A levels were detected by enzyme-linked immunosorbent assays. IFN-γ, mTOR and RAR-related orphan receptor (ROR)γt mRNA levels were evaluated by the real-time polymerase chain reaction.

Results

Elevated p-mTOR expression in CD8+ T cells and lung tissue was accompanied by the enhanced Tc1 and Tc17 cell responses in lungs of mice exposed to cigarette smoke. Rapamycin reduced inflammatory cells in BALF and decreased MLI, DI and MAA in lungs. Rapamycin decreased p-mTOR expression, and down-regulation of mTOR and RORγt mRNA levels along with the attenuation of Tc1 and Tc17 cell responses in mice with emphysema.

Conclusions

The mTOR was activated in CD8+ T cells accompanied by the enhanced Tc1 and Tc17 cell responses in cigarette smoke-related pulmonary inflammation. Rapamycin ameliorated emphysema and attenuated Tc1 and Tc17 cell responses probably caused by inhibiting mTOR in cigarette smoke-exposed mice.

Keywords

Rapamycin Cigarette smoke CD8+IFN-γ+ T cells CD8+IL-17+ T cells Chronic obstructive pulmonary disease Emphysema 

Notes

Acknowledgements

This study was funded by grants from the National Natural Science Foundation of China (Grant numbers 81770041 and 81800037).

Compliance with ethical standards

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the author(s).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hui Zhang
    • 1
  • Xiu Zhou
    • 1
  • Xin Chen
    • 1
  • Yuanzhen Lin
    • 1
  • Shilin Qiu
    • 1
  • Yun Zhao
    • 1
  • Qiya Tang
    • 1
  • Yi Liang
    • 1
  • Xiaoning Zhong
    • 1
    Email author
  1. 1.Department of Respiratory and Critical Care MedicineThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina

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