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UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance
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  • Published: 05 February 2026

UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance

  • Yuxing Gong1,2 na1,
  • Yufei Ding3,4 na1,
  • Jingyi Yang1,4,
  • Tao Ding1,2,
  • Bin Li1,2,
  • Junfeng Ma5,
  • Wahid Shah2,6,
  • Youcai Deng7,
  • Ping Duan8,9,
  • Yu Zhang1 &
  • …
  • Yuan Gao2,6 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cell biology
  • Diseases
  • Immunology
  • Stem cells

Abstract

Dry eye disease (DED) is a chronic ocular surface disorder characterized by Th17/Treg cells imbalance, particularly prevalent among elderly females. Current treatment approaches are evolving from merely providing symptomatic relief to targeting immune dysfunction. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated the ability to modulate the immune response and promote corneal epithelial cell regeneration in DED. Nonetheless, the precise mechanism through which MSC-Exos exert these effects is not yet fully understood. Consequently, the objective of this study was to explore the mechanisms behind the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) in a murine model of DED. We discovered that UCMSC-Exos stimulated human corneal epithelial cell lines wound healing in vitro. The topical or systemic administration of UCMSC-Exos significantly altered cytokine expression by neutrophils, leading to a reduction in proinflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. This shift in the cytokine profile reestablished the Treg/Th17 cells balance, resulting in decreased inflammation and alleviation of DED symptoms, with younger mice showing more pronounced benefits. These results highlight the potential of UCMSC-Exos as a therapeutic approach for DED that modulates immune dysregulation and enhances ocular surface repair.

Data availability

The datasets generated and analysed during this study are available in the the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository under accession number GSE316045.

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Acknowledgements

We thank all staff for collecting experimental data for this study.

Funding

Our work was supported by The National Key Research and Development Program of China grant 2019YFA0111200 (to Y. Gao); The National Key Research and Development Program of China grant 2020YFA0113500 (to Y. Deng); National Natural Science Foundation of China grant 82371047 (to Y. Gao); Joint Funds of the National Natural Science Foundation of China grant U23A20436 (to Y. Gao); The Key Program of Shanxi Province grant 202302130501008 (to Y. Gao); Shanxi Provincial Science Fund for Distinguished Young Scholars grant 202103021221008 (to Y. Gao); Key Innovation Teams of Shanxi Province grant 202204051001023 (to Y. Gao); Shanxi Provincial Foundation for Leaders of Disciplines in Science grant 2024Q014 (to Y. Gao); The Shanxi Provincial Foundation for Returned Scholars 2022 -117 (to Y. Gao); and Natural Science Foundation of Chongqing City grant CSTB2022NSCQ-MSX0833 (to P. Duan).

Author information

Author notes

  1. Yuxing Gong and Yufei Ding contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Yuxing Gong, Jingyi Yang, Tao Ding, Bin Li & Yu Zhang

  2. Translational Medicine Research Center, Shanxi Medical University, Taiyuan, 030001, China

    Yuxing Gong, Tao Ding, Bin Li, Wahid Shah & Yuan Gao

  3. Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Yufei Ding

  4. Academy of Medical Sciences, Shanxi Medical University, Jinzhong, 030006, Shanxi, China

    Yufei Ding & Jingyi Yang

  5. Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400038, China

    Junfeng Ma

  6. Shanxi Eye Hospital Affiliated to Shanxi Medical University, Taiyuan, 030002, China

    Wahid Shah & Yuan Gao

  7. Department of Pharmacology, College of Pharmacy, Army Medical University, Chongqing, 400038, China

    Youcai Deng

  8. Southwest Hospital/Southwest Eye Hospital, Army Medical University, Chongqing, 400038, China

    Ping Duan

  9. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China

    Ping Duan

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  1. Yuxing Gong
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Contributions

YG-X Contributed to conceptualization; YG-X, YD-F, J.Y., T.D. and J.M. Conducted the experiments; YG-X, YD-F, B.L., W.S., Y.D. and Y.Z. Wrote the manuscript; YG-X, YD-F, J.Y., T.D., J.M. Contributed to methodology, validation and formal analysis; All the authors contributed to manuscript writing-original draft preparation; YG-X, YD-F, Y.D., P.D., and Y.G. Contributed to revise the manuscript. Y.G. Contributed to editing and supervision of the project; Y.G. Contributed to project administration and funding acquisition. All authors contributed to the article and approved the submitted version. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Yu Zhang or Yuan Gao.

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Competing interests

The authors declare no competing interests.

Ethical approval

Human umbilical cord mesenchymal stem cells (UCMSCs) were approved by Shanxi Medical University (approval number: 2023SJL66) and conducted in accordance with the local legislation and institutional requirements. All animal experiments were approved by the Animal Care Committee of Shanxi Medical University (approval number: 2023-133) and conducted according to the institution’s laboratory animal welfare guidelines.

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Gong, Y., Ding, Y., Yang, J. et al. UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38010-y

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  • Received: 23 July 2025

  • Accepted: 28 January 2026

  • Published: 05 February 2026

  • DOI: https://doi.org/10.1038/s41598-026-38010-y

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Keywords

  • Dry eye disease
  • Exosomes
  • Umbilical cord mesenchymal stem cells
  • Neutrophils
  • Th17/Treg cells balance
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