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miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity

Cellular & Molecular Immunology volume 16, pages 112–125 (2019)Cite this article

Abstract

As an important component of innate immunity, human circulating γδ T cells function in rapid responses to infections and tumorigenesis. MicroRNAs (miRNAs) play a critical regulatory role in multiple biological processes and diseases. Therefore, how the functions of circulating human γδ T cells are regulated by miRNAs merits investigation. In this study, we profiled the miRNA expression patterns in human peripheral γδ T cells from 21 healthy donors and identified 14 miRNAs that were differentially expressed between peripheral αβ T cells and γδ T cells. Of the 14 identified genes, 7 miRNAs were downregulated, including miR-150-5p, miR-450a-5p, miR-193b-3p, miR-365a-3p, miR-31-5p, miR-125b-5p and miR-99a-5p, whereas the other 7 miRNAs were upregulated, including miR-34a-5p, miR-16-5p, miR-15b-5p, miR-24-3p, miR-22-3p, miR-22-5p and miR-9-5p, in γδ T cells compared with αβ T cells. In subsequent functional studies, we found that both miR-125b-5p and miR-99a-5p downregulated γδ T cell activation and cytotoxicity to tumor cells. Overexpression of miR-125b-5p or miR-99a-5p in γδ T cells inhibited γδ T cell activation and promoted γδ T cell apoptosis. Additionally, miR-125b-5p knockdown facilitated the cytotoxicity of γδ T cells toward tumor cells in vitro by increasing degranulation and secretion of IFN-γ and TNF-α. Our findings improve the understanding of the regulatory functions of miRNAs in γδ T cell activation and cytotoxicity, which has implications for interventional approaches to γδ T cell-mediated cancer therapy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31500725, 81673010, 91542117, 81471574 and 31471016), CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses (2016ZX310180-5 and 2017PT31004), the CAMS Initiative for Innovative Medicine (2016-I2M-1-008), the National Key Research and Development Program of China (2016YFA0101001 and 2016YFC0903900), Peking Union Medical College Foundation (No. 3332015111), and Peking Union Medical College Science Foundation for Young Scientists (No. 3332015109). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr Austin Cape at ASJ Editors for the editing and comments.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Research Center on Pediatric Development and Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, 100005, Beijing, China

    Yuli Zhu, Siya Zhang, Zinan Li, Huaishan Wang, Zhen Li, Yu Hu, Hui Chen, Lianxian Cui, Jianmin Zhang & Wei He

  2. Institute of blood transfusion, Qingdao Blood Center, 266071, Qingdao, China

    Yuli Zhu

  3. Department of Rheumatology & Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China

    Xuan Zhang

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Zhu, Y., Zhang, S., Li, Z. et al. miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity. Cell Mol Immunol 16, 112–125 (2019). https://doi.org/10.1038/cmi.2017.164

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