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Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro

BACKGROUND: Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance. METHODS: This study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous tee...

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Autores principales: Dai, Yu-Yang, Ni, Si-Yang, Ma, Ke, Ma, Yu-Shi, Wang, Zhi-Shi, Zhao, Xiu-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341645/
https://www.ncbi.nlm.nih.gov/pubmed/30670101
http://dx.doi.org/10.1186/s13287-019-1134-z
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author Dai, Yu-Yang
Ni, Si-Yang
Ma, Ke
Ma, Yu-Shi
Wang, Zhi-Shi
Zhao, Xiu-Li
author_facet Dai, Yu-Yang
Ni, Si-Yang
Ma, Ke
Ma, Yu-Shi
Wang, Zhi-Shi
Zhao, Xiu-Li
author_sort Dai, Yu-Yang
collection PubMed
description BACKGROUND: Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance. METHODS: This study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3 days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3(+) Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-β(1), PGE(2)) in the immunomodulatory mechanism, a cytokine neutralization assay was performed. RESULTS: Nasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG(1) levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-γ was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-γ, IL-10, PGE(2), and TGF-β(1); decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-β(1) partly relieved the immunosuppression of SHEDs, but blocking PGE(2) did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro. CONCLUSION: These results suggest that SHEDs could correct the CD4(+) T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1134-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-63416452019-01-24 Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro Dai, Yu-Yang Ni, Si-Yang Ma, Ke Ma, Yu-Shi Wang, Zhi-Shi Zhao, Xiu-Li Stem Cell Res Ther Research BACKGROUND: Several studies have demonstrated that mesenchymal stem cells can ameliorate the inflammation of allergic rhinitis (AR) and correct the Th1/Th2 immune imbalance. METHODS: This study was performed to explore the immunomodulation properties of stem cells from human exfoliated deciduous teeth (SHEDs) in the treatment of AR in vivo and in vitro. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and then SHEDs or bone marrow mesenchymal stem cells (BMMSCs) were injected intravenously before challenge. We evaluated nasal symptoms, inflammatory infiltration of nasal mucosa, immunoglobulin secretion, cytokine production, and mRNA expression in the spleen. In addition, peripheral blood mononuclear cells (PBMCs) from AR patients were cultured with SHEDs or BMMSCs in the presence of phytohemagglutinin (PHA). PBMCs cultured alone with or without PHA served as controls. After 3 days of culture, we examined the effect of SHEDs on T lymphocyte proliferation, cytokine secretion, and the proportion of Foxp3(+) Treg cells via flow cytometry. Finally, to determine the role of soluble factors (TGF-β(1), PGE(2)) in the immunomodulatory mechanism, a cytokine neutralization assay was performed. RESULTS: Nasal symptoms and inflammatory infiltration were significantly reduced after SHED administration. The OVA-specific IgE and IgG(1) levels in serum were significantly decreased, and the increased IL-4, IL-5, IL-13, and IL-17A levels in the spleen after OVA challenge were markedly downregulated, while the level of IFN-γ was upregulated by SHED administration. The mRNA expression levels also changed correspondingly. SHEDs significantly inhibited the proliferation of T lymphocytes; increased the levels of IFN-γ, IL-10, PGE(2), and TGF-β(1); decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-β(1) partly relieved the immunosuppression of SHEDs, but blocking PGE(2) did not. In addition, SHEDs were superior to BMMSCs in inhibiting the Th2 immune response in vivo and inducing the expansion of Treg cells in vitro. CONCLUSION: These results suggest that SHEDs could correct the CD4(+) T cell immune imbalance via Treg cells and may be potential therapeutic agents for the treatment of allergic diseases, such as AR, in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-019-1134-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-22 /pmc/articles/PMC6341645/ /pubmed/30670101 http://dx.doi.org/10.1186/s13287-019-1134-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Dai, Yu-Yang
Ni, Si-Yang
Ma, Ke
Ma, Yu-Shi
Wang, Zhi-Shi
Zhao, Xiu-Li
Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title_full Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title_fullStr Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title_full_unstemmed Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title_short Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro
title_sort stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via treg cells in vivo and in vitro
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341645/
https://www.ncbi.nlm.nih.gov/pubmed/30670101
http://dx.doi.org/10.1186/s13287-019-1134-z
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