Kyung-Ah Cho1, Je-Eun Cha1, Jungwoo Kim1, Yu-Hee Kim2, Kyung-Ha Ryu3, So-Youn Woo4. 1. Department of Microbiology, College of Medicine, Ewha Womans University, 25, Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. 2. Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, Gangseo-Gu, Seoul, 07804, Republic of Korea. 3. Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, 07804, Republic of Korea. 4. Department of Microbiology, College of Medicine, Ewha Womans University, 25, Magokdong-ro 2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea. soyounwoo@ewha.ac.kr.
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.
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.
Authors: Hae Mi Joo; Su Jin Kang; Seon Young Nam; Kwang Hee Yang; Cha Soon Kim; In Kyung Lee; Ji Young Kim Journal: PLoS One Date: 2015-08-28 Impact factor: 3.240