Abstract
BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved.MethodsEighty percent confluent stem cells were replenished with serum-free Dulbecco’s modified Eagle’s medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were categorized into the following groups (n = 6 each): non-treatment, Dulbecco’s modified Eagle’s medium (−), BMMSC-CM, and DPSC-CM. Histological analysis of the salivary glands was performed. The gene and protein expression levels of cytokines associated with T helper subsets in the submandibular glands (SMGs) were evaluated.ResultsDPSC-CM contained more secreted factors with tissue-regenerating mechanisms, such as cell proliferation, anti-inflammatory effects, and immunomodulatory effects. DPSC-CM was more effective in suppressing the activated T cells than other groups in the flow cytometric analysis. The stimulated salivary flow rate increased in SS mice with DPSC-CM compared with that in the other groups. In addition, the number of inflammation sites in SMGs of the mice administered with DPSC-CM was lower than that in the other groups. The expression levels of interleukin (Il)-10 and transforming growth factor-β1 were upregulated in the DPSC-CM group, whereas those of Il-4 and Il-17a were downregulated. The DPSC-CM-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups.ConclusionsThese results indicated that DPSC-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen.
Highlights
Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands
These results indicated that dental pulp stem cells (DPSCs)-CM ameliorated SS by promoting Treg cell differentiation and inhibiting Th17 cell differentiation in the mouse spleen
Flow cytometric analysis suggested that the addition of DPSC-CM could decrease the proportion of CD3+CD25+ or CD3+CD69+ cells (Fig. 2a) and CD4+CD25+ or CD4+CD69+ cells (Fig. 2b) and that DPSC-CM was more effective in suppressing T cell activation than bone marrow mesenchymal stem cells (BMMSCs)-CM
Summary
Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. Sjögren’s syndrome (SS) is a chronic, systemic autoimmune disorder characterized by the inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands [1]. T cells (mostly CD4expressing T helper [Th] cells) form a large part of the lymphocytic infiltrate observed in the salivary and lacrimal gland tissues of SS patients, during the earlier stages of the disease [1, 2]. Treg cells suppress autoreactive lymphocytes via cell–cell contact or the release of soluble mediators, such as IL-10 and transforming growth factor-β1 (TGF-β1) [13]
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