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Regulatory T cells regulate the distribution of natural killer T cells through CD39 signal transduction in asthma

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Abstract

Natural killer T cells (NKT cells) and regulatory T cells (Treg cells) are two important immune regulatory cells which both play critical roles in asthma. Our previous experiments revealed that activation of Treg cells suppressed NKT cells in asthma. However, the possible regulatory effects and the mechanisms linking Treg cells and NKT cells remain poorly understood. The current study was designed to further investigate the regulatory effect and its possible mechanisms of Treg cells on NKT cells function, especially the distribution of NKT cells. Regulatory T cell (Treg), responder T cell (Teff) and Natural killer T cell (NKT) were isolated and purified. After Lentivirus carrying CD39 (Le-CD39) was transfected into Treg cells, the immune phenotype of Treg cells was changed and the suppressive effect of Treg cells on Teff cells with an activation of Treg cells was enhanced, marking with a high expression level of interleukin 10 (IL-10) and transforming growth factor β (TGF-β). Up-regulation of CD39 expression led to lower ATP level in cell culture supernatant. To further explore its function in asthma, we introduced an ovalbumin (OVA)-induced mice model of asthma. And the data showed that up-regulation of CD39 remarkably alleviated OVA-induced hallmarks of the asthma and increased NKT cells in the spleen and peripheral blood; however, decreased NKT cells in the lung. Furthermore, up-regulation of CD39 decreased the levels of interleukin 4 (IL-4) and interferon γ (IFN-γ) in the lung of OVA-treated mice. Our results strongly suggest that Treg cells could be activated by CD39 signal transduction and then affected the distribution of NKT cells in the OVA-induced mice model of asthma.

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Funding

This study was financially supported by Scientific research project of Shanghai health and Family Planning Commission (no. 201640018).

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Authors and Affiliations

  1. Department of Pediatrics, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 2000 Jiangyue Road, Minhang District, Shanghai, 201112, People’s Republic of China

    Yanming Lu, Yaqin Li, Wenjing Zhou, Bo Ding & Qing Yu

Authors
  1. Yanming Lu
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  2. Yaqin Li
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  3. Wenjing Zhou
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  4. Bo Ding
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  5. Qing Yu
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Contributions

YL carried out the study and the data statistics, YL participated in study design and drafted the manuscript, WZ supervised the study, BD and QY contributed to the scientific discussion of the data.

Corresponding author

Correspondence to Yanming Lu.

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Conflict of interest

The authors have declared that no competing interests exist.

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This study is approved by all authors for publication.

Ethical approval

All animal experiments were approved by Renji Hospital, School of Medicine, Shanghai Jiao Tong University Institutional Animal Ethics Committee and were carried out according to the institutional guidelines from the Principles of Laboratory Animal Care of Renji Hospital, School of Medicine, Shanghai Jiao Tong University.

Availability of data and supporting materials

The datasets supporting the conclusions of this article are included within the article. Any additional information related to this study is available from the author for correspondence upon reasonable request.

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Lu, Y., Li, Y., Zhou, W. et al. Regulatory T cells regulate the distribution of natural killer T cells through CD39 signal transduction in asthma. Human Cell 32, 141–149 (2019). https://doi.org/10.1007/s13577-018-00226-0

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  • DOI: https://doi.org/10.1007/s13577-018-00226-0

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