Ann Dermatol.  2021 Oct;33(5):402-408. 10.5021/ad.2021.33.5.402.

Toll‐Like Receptor 7 (TLR7) Mediated Transcriptomic Changes on Human Mast Cells

• Cho KA
• Choi DW
• Park M
• Kim YH
• Woo SY

• KMID: 2519924
• DOI: http://doi.org/10.5021/ad.2021.33.5.402

Abstract

Background
Mast cells are skin immune sentinels located in the upper dermis, where wheal formation and sensory nerve stimulation take place. Skin inflammation is occasionally accompanied by mast cell-driven responses with wheals, angioedema, or both. Immunoglobulin E (IgE) antibodies are regarded as typical stimuli to drive mast cell activation. However, various causative factors, including microbial infections, can drive IgE-independent mast cell response. When infected, the innate immunity orchestrates an immune response by activating receptor signaling via Toll-like receptors (TLRs).
Objective
In this study, we determined the effect of TLR7 stimulation on mast cells to investigate the possible mechanism of IgE-independent inflammatory response.
Methods
Human mast cell (HMC) line, HMC-1 cells were treated with TLR7 agonist and the morphologic alteration was observed in transmission electron microscopy. Further, TLR7 agonist treated HMC-1 cells were conducted to RNA sequencing to compare transcriptomic features.
Results
HMC-1 cells treated with TLR7 agonist reveals increase of intracellular vesicles, lipid droplets, and ribosomes. Also, genes involved in pro-inflammatory responses such as angiogenesis are highly expressed, and Il12rb2 was the most highly upregulated gene.
Conclusion
Our data suggest that TLR7 signaling on mast cells might be a potential therapeutic target for mast cell-driven, IgE-independent skin inflammation.

Keyword

Mast cell; Skin inflammation; Toll‐like receptor 7