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

Tissue Eng Regen Med. 2022 Feb;19(1):117-129. doi: 10.1007/s13770-021-00395-4. Epub 2021 Nov 18.

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.

Keywords: Exosomes; Mast cell; Mesenchymal stem cell; TLR7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exosomes* / metabolism
  • Mast Cells / metabolism
  • Membrane Glycoproteins / immunology*
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 7 / metabolism

Substances

  • Membrane Glycoproteins
  • MicroRNAs
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7