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

Abstract

Abstract 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-β1, PGE2) 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 IgG1 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, PGE2, and TGF-β1; decreased the levels of IL-4 and IL-17A; and induced the expansion of Treg cells in the coculture system. The neutralization of TGF-β1 partly relieved the immunosuppression of SHEDs, but blocking PGE2 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.

Keywords

• Allergic rhinitis
• Stem cells from human exfoliated deciduous teeth
• Regulatory T cells
• Transforming growth factor beta
• Immunoregulation