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Mesenchymal Stem Cell-Derived Exosomes Attenuate TLR7-Mediated Mast Cell Activation

Abstract

Background:

Mast cells are immune sentinels in the skin that respond to a wide range of pathological and environmental stimuli; they owe their function to the expression of Toll-like receptors (TLRs). We previously found that tonsil-derived mesenchymal stem cells (T-MSCs) were able to effectively attenuate TLR7-mediated skin inflammation in mice, which was accompanied by an increase in mast cell number. The present study investigated whether T-MSC extracellular vesicles, such as exosomes, are able to regulate mast cell activation in response to TLR7 stimulation.

Methods:

The HMC-1 human mast cell line was treated with a TLR7 agonist in the presence or absence of T-MSC exosomes, and the levels of expressed inflammatory cytokines were assessed. Additionally, mice were repeatedly injected with a TLR7 agonist with or without interval treatments with T-MSC exosomes and assessed dermal distribution of mast cells and related immune cells.

Results:

We showed that T-MSC exosomes containing microRNAs that target inflammatory cytokines significantly reduced the expression of inflammatory cytokines in TLR7 agonist-treated HMC-1 cells. In addition, T-MSC exosomes inhibited the increase in the number of both dermal mast cells and CD14-positive cells in TLR7 agonist-treated mice.

Conclusion:

Our data suggest that T-MSC exosomes have regulatory effects on mast cell activation under inflammatory conditions, including TLR7 stimulation.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (Nos. NRF-2020R1C1C1012769 and NRF-2021R1A2C1012551).

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Correspondence to So-Youn Woo.

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The authors declare that they have no conflict of interest.

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The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Ewha Woman’s University, College of Medicine (EUM 20-024).

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Cite this article

Cho, KA., Cha, JE., Kim, J. et al. Mesenchymal Stem Cell-Derived Exosomes Attenuate TLR7-Mediated Mast Cell Activation. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00395-4

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Keywords

  • Mast cell
  • TLR7
  • Mesenchymal stem cell
  • Exosomes