Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Blood. 2012 Oct 11;120(15):3142-51. doi: 10.1182/blood-2011-11-391144. Epub 2012 Aug 27.
Sjögren syndrome (SS) is a systemic autoimmune disease characterized by dry mouth and eyes, and the cellular and molecular mechanisms for its pathogenesis are complex. Here we reveal, for the first time, that bone marrow mesenchymal stem cells in SS-like NOD/Ltj mice and human patients were defective in immunoregulatory functions. Importantly, treatment with mesenchymal stem cells (MSCs) suppressed autoimmunity and restored salivary gland secretory function in both mouse models and SS patients. MSC treatment directed T cells toward Treg and Th2, while suppressing Th17 and Tfh responses, and alleviated disease symptoms. Infused MSCs migrated toward the inflammatory regions in a stromal cell-derived factor-1-dependent manner, as neutralization of stromal cell-derived factor-1 ligand CXCR4 abolished the effectiveness of bone marrow mesenchymal stem cell treatment. Collectively, our study suggests that immunologic regulatory functions of MSCs play an important role in SS pathogenesis, and allogeneic MSC treatment may provide a novel, effective, and safe therapy for patients with SS.
干燥综合征（SS）是一种系统性自身免疫性疾病，其特征为口干和眼干，其发病机制的细胞和分子机制复杂。在这里，我们首次揭示，SS 样 NOD/Ltj 小鼠和人类患者的骨髓间充质干细胞在免疫调节功能上存在缺陷。重要的是，间充质干细胞（MSCs）治疗抑制了自身免疫，并恢复了两种小鼠模型和 SS 患者的唾液腺分泌功能。MSC 治疗使 T 细胞向 Treg 和 Th2 分化，同时抑制 Th17 和 Tfh 反应，并缓解疾病症状。输注的 MSCs 以基质细胞衍生因子-1（stromal cell-derived factor-1，SDF-1）依赖性方式向炎症区域迁移，而基质细胞衍生因子-1 配体 CXCR4 的中和则消除了骨髓间充质干细胞治疗的有效性。总之，我们的研究表明，MSCs 的免疫调节功能在 SS 的发病机制中起重要作用，同种异体 MSC 治疗可能为 SS 患者提供一种新颖、有效且安全的治疗方法。
