Tian Jie, Hong Yue, Zhu Qiugang, Zhou Huimin, Zhang Yidan, Shen Ziwei, Guo Hongye, Zhang Yue, Ai Xiangyan, Zhao Futao, Rui Ke, Xu Huaxi, Wang Shengjun
Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China.
Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Front Immunol. 2020 Dec 22;11:604607. doi: 10.3389/fimmu.2020.604607. eCollection 2020.
Primary Sjögren's syndrome (pSS) is a progressive systemic autoimmune disease characterized by lymphocytic infiltrates in exocrine glands, leading to the injury of salivary and lachrymal glands. Mesenchymal stem cells (MSCs) have been demonstrated to exert great potential in the treatment of various autoimmune diseases. Although MSCs have provide an effective therapeutic approach for SS treatment, the underlying mechanisms are still elusive. Our previous study has shown the reduced suppressive capacity of myeloid-derived suppressor cells (MDSCs) advanced the progression of experimental Sjögren's syndrome (ESS). In this study, we found that BM-MSCs significantly enhanced the suppressive function of MDSCs with high levels of Arginase and NO, decreased the levels of CD40, CD80, CD86, and MHC-II expression on MDSCs, thus attenuating the disease progression in ESS mice. Furthermore, the enhanced suppressive function of MDSCs was mediated by BM-MSC-secreted TGF-β, and the therapeutic effect of BM-MSCs in inhibiting ESS was almost abolished after silencing TGF-β in BM-MSCs. Taken together, our results demonstrated that BM-MSCs alleviated the ESS progression by up-regulating the immunosuppressive effect of MDSCs through TGF-β/Smad pathway, offering a novel mechanism for MSCs in the treatment of pSS.
原发性干燥综合征（pSS）是一种进行性全身性自身免疫性疾病，其特征是外分泌腺出现淋巴细胞浸润，导致唾液腺和泪腺受损。间充质干细胞（MSCs）已被证明在治疗各种自身免疫性疾病方面具有巨大潜力。尽管MSCs为干燥综合征的治疗提供了一种有效的治疗方法，但其潜在机制仍不清楚。我们之前的研究表明，髓源性抑制细胞（MDSCs）抑制能力的降低促进了实验性干燥综合征（ESS）的进展。在本研究中，我们发现骨髓间充质干细胞（BM-MSCs）显著增强了MDSCs的抑制功能，使其精氨酸酶和一氧化氮水平升高，降低了MDSCs上CD40、CD80、CD86和MHC-II的表达水平，从而减轻了ESS小鼠的疾病进展。此外，MDSCs增强的抑制功能由BM-MSC分泌的转化生长因子-β（TGF-β）介导，在BM-MSCs中沉默TGF-β后，BM-MSCs抑制ESS的治疗效果几乎完全消失。综上所述，我们的结果表明，BM-MSCs通过TGF-β/ Smad信号通路上调MDSCs的免疫抑制作用，从而减轻ESS的进展，为MSCs治疗pSS提供了一种新机制。
