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BMSC-derived exosomes regulate the Treg/Th17 balance through the miR-21-5p/TLR4/MyD88/NF-κB pathway to alleviate dry eye symptoms in mice

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Abstract

Bone marrow mesenchymal stem cell (BMSC)–derived exosomes (BMSC-Exos) have a variety of biological functions and are extensively involved in the regulation of inflammatory diseases, as well as tissue repair and regeneration. However, the mechanism of action of these compounds in dry eye disease (DED) in mice is still unclear. This study demonstrated that the Treg/Th17 ratio was strongly imbalanced in DED clinical samples. BMSC-Exos can modulate the Treg/Th17 balance, improve the integrity of the corneal epithelial layer, and ameliorate DED progression in mice. Mechanistically, BMSC-Exos dramatically decreased the levels of IL-17 and IL-22; increased the levels of IL-4, IL-10, and TGF-β1; and increased tear secretion and the number of goblet cells in the conjunctiva in mice, thus alleviating the progression of DED. This effect is achieved by BMSC-Exos through the delivery of miR-21-5p to target and restrain TLR4, thereby restraining the MyD88/NF-κB pathway. Our study showed that the upregulation of miR-21-5p in BMSC-Exos may be a therapeutic target for DED. These findings support new ideas and a basis for treating DED, as well as for further study of the application value of exosomes in alleviating DED.

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Data availability

The datasets that were used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the Yunnan Basic Research Program (202301AY070001-156), the National Natural Science and Technology Foundation project (82360201), the Health Research Project of Kunming Health Commission (2020–07-02–112), the Yunnan Province Young and Middle-Aged Academic and Technical Leaders Reserve Talent Project (02405AC350103), the Kunming Health Science and Technology Personnel Training Project, and the “ten hundred thousand” project (2020-SW [province]-01).

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Author notes

  1. Dandan Zhao and Hao Ji contributed equally to this study.

Authors and Affiliations

  1. Department of Ophthalmology, Yan’an Hospital of Kunming City, Kunming, Yunnan, 650051, China

    Dandan Zhao, Hongxia Zhao, Yanze Xu & Yang He

  2. Department of Information, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China

    Hao Ji

  3. Department of Ophthalmology, Kunming Medical University, Kunming, Yunnan, 650500, China

    Anni He

Authors
  1. Dandan Zhao
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  2. Hao Ji
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  3. Hongxia Zhao
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  4. Yanze Xu
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  5. Anni He
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  6. Yang He
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Contributions

All of the authors contributed substantially to this manuscript. Conceptualization, Dandan Zhao and Hao Ji; methodology, Dandan Zhao; software, Hongxia Zhao and Yanze Xu; validation, Anni He; formal analysis, Dandan Zhao; investigation, Dandan Zhao, Hao Ji, and Yang He; resources, Yang He; writing—original draft preparation, Dandan Zhao and Hao Ji; writing—review and editing, Yang He; visualization, Hongxia Zhao, Yanze Xu, and Anni He; supervision, Yang He; funding acquisition, Yang He. All of the authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yang He.

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Ethics approval and consent to participate

Informed consent was obtained from all of the patients. The experiments were approved by the Medical Ethics Committee of Kunming Yan’an Hospital (approval number: 2022–056-01), and all of the methods/studies were conducted in accordance with the Declaration of Helsinki. All of the animal experiments were approved by the Animal Ethics and Welfare Committee of Kunming Yan’an Hospital (approval number: 2022051).

Competing interests

The authors declare no competing interests.

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Zhao, D., Ji, H., Zhao, H. et al. BMSC-derived exosomes regulate the Treg/Th17 balance through the miR-21-5p/TLR4/MyD88/NF-κB pathway to alleviate dry eye symptoms in mice. In Vitro Cell.Dev.Biol.-Animal (2024). https://doi.org/10.1007/s11626-024-00910-6

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  • DOI: https://doi.org/10.1007/s11626-024-00910-6

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