Su Yingying, Gu Yi, Wu Ruiqing, Wang Hao
Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Pediatrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Stem Cells Int. 2018 Aug 2;2018:9837035. doi: 10.1155/2018/9837035. eCollection 2018.
Mesenchymal stem cells (MSCs) treatment has emerged as a promising approach for treating Sjögren's syndrome (SS). Impaired immunoregulatory activities of bone marrow mesenchymal stem cells (BMMSCs) are found in both SS patients and animal models, and the underlying mechanism is poorly understood. Increased expression of BMP6 is reported to be related to SS. The aim herein was to determine the effects of BMP6 on BMMSCs function. BMMSCs were isolated from SS patients and NOD mice and showed a high level of BMP6 expression. The effects of BMP6 on BMMSCs function were investigated using BMMSCs differentiation and and T cell proliferation and polarization assays. BMP6 increased osteogenic differentiation of BMMSCs and inhibited the immunomodulatory properties of BMMSCs. BMP6 enhanced T cell proliferation and Th1/Th17 differentiation in a T cell-BMMSC coculture system. Mechanistically, BMP6 downregulated PGE2 and upregulated IFN-gamma via Id1 (inhibitor of DNA-binding protein 1). Neutralizing BMP6 and knockdown of Id1 could restore the BMMSCs immunosuppressive function both and . The present results suggest a novel role of Id1 in BMP-mediated MSCs function, which may contribute to a better understanding of the mechanism of action of MSCs in treating autoimmune diseases.
间充质干细胞（MSCs）治疗已成为治疗干燥综合征（SS）的一种有前景的方法。在SS患者和动物模型中均发现骨髓间充质干细胞（BMMSCs）的免疫调节活性受损，但其潜在机制尚不清楚。据报道，BMP6表达增加与SS有关。本文旨在确定BMP6对BMMSCs功能的影响。从SS患者和NOD小鼠中分离出BMMSCs，其BMP6表达水平较高。使用BMMSCs分化以及T细胞增殖和极化试验研究了BMP6对BMMSCs功能的影响。BMP6增加了BMMSCs的成骨分化并抑制了BMMSCs的免疫调节特性。在T细胞-BMMSC共培养系统中，BMP6增强了T细胞增殖和Th1/Th17分化。机制上，BMP6通过Id1（DNA结合蛋白1抑制剂）下调PGE2并上调IFN-γ。中和BMP6和敲低Id1均可恢复BMMSCs的免疫抑制功能。目前的结果表明Id1在BMP介导的MSCs功能中具有新作用，这可能有助于更好地理解MSCs治疗自身免疫性疾病的作用机制。
