Mesenchymal Stem Cell Enhances the Function of MDSCs in Experimental Sjögren Syndrome.
Mesenchymal Stem Cell Enhances the Function of MDSCs in Experimental Sjögren Syndrome.
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DOI：
10.3389/fimmu.2020.604607
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发表时间：
2020
影响因子：
7.3
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Tian J;Hong Y;Zhu Q;Zhou H;Zhang Y;Shen Z;Guo H;Zhang Y;Ai X;Zhao F;Rui K;Xu H;Wang S
原发性干燥综合征（Primary Sjögren's syndrome，pSS）是一种进行性全身性自身免疫性疾病，其特征是外分泌腺淋巴细胞浸润，导致唾液腺和泪腺损伤。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）在治疗各种自身免疫性疾病方面具有巨大的潜力。虽然间充质干细胞为SS的治疗提供了一种有效的治疗方法，但其潜在的机制仍不清楚。我们先前的研究表明，髓源性抑制细胞（MDSC）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BM-MSCs显著增强了具有高水平精氨酸酶和NO的MDSC的抑制功能，降低了MDSC上的CD 40、CD 80、CD 86和MHC-II表达水平，从而减缓了ESS小鼠的疾病进展。BM-MSC分泌的TGF-β介导了MDSCs对ESS的抑制作用，沉默TGF-β后，BM-MSC抑制ESS的作用几乎消失。综上所述，我们的研究结果表明BM-MSCs通过TGF-β/Smad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提供了一种新的机制。
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.