骨形态发生蛋白 6 对干燥综合征唾液腺间充质干细胞免疫调节功能的影响。
Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjögren's Syndrome.
机构信息
1 Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology , Beijing, China .
2 Mucosal Immunology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, Maryland.
出版信息
Stem Cells Dev. 2018 Nov 15;27(22):1540-1548. doi: 10.1089/scd.2017.0161.
Abstract
Sjögren's syndrome (SS) is characterized by autoimmune activation and loss of function in the salivary glands. Recent studies reported that bone morphogenetic protein 6 (BMP6), which is a member of transforming growth factor beta (TGF-β) superfamily, was highly expressed in SS patients. To investigate the role of BMP6 in SS, we treated the salivary gland-derived mesenchymal stem cells (SGMSCs) with BMP6 and found that BMP6 could impair immunomodulatory properties of normal SGMSCs by downregulating the Prostaglandin E2 synthase through DNA-binding protein inhibitor-1. Neutralizing the BMP6 could significantly restore the SGMSC's immunoregulatory function in vitro and delay the SS disease activity in vivo. In conclusion, BMP6 could not only affect the secreting function of epithelial cells in the salivary gland but also influence the immunomodulatory properties of SGMSCs, which may trigger or enhance the autoimmune reflection in SS.
摘要
干燥综合征（SS）的特征是自身免疫激活和唾液腺功能丧失。最近的研究报告称，骨形态发生蛋白 6（BMP6）是转化生长因子-β（TGF-β）超家族的成员，在 SS 患者中高度表达。为了研究 BMP6 在 SS 中的作用，我们用 BMP6 处理唾液腺来源的间充质干细胞（SGMSCs），发现 BMP6 可以通过下调前列腺素 E2 合酶来损害正常 SGMSCs 的免疫调节特性，通过 DNA 结合蛋白抑制剂-1。中和 BMP6 可显著恢复 SGMSC 的体外免疫调节功能，并延迟体内 SS 疾病活动。总之，BMP6 不仅可以影响唾液腺上皮细胞的分泌功能，还可以影响 SGMSCs 的免疫调节特性，这可能引发或增强 SS 中的自身免疫反应。
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