IFN-α调控MSCs上调nTreg抑制DCs在SLE治疗中的作用及机制

系统性红斑狼疮(SLE)是一种常见的自身免疫病，异体间充质干细胞(MSCs) 移植治疗SLE是一项新技术。前期研究已观察到异体MSCs移植治疗后，SLE患者PBMC中I型干扰素诱导基因表达水平显著下降，但具体机制尚不清楚。我们发现体外IFN-α显著刺激脐带MSCs表达TGF-β上调Treg，推测IFN-α在启动脐带MSCs的免疫调控中发挥重要作用。本课题拟进一步通过体内外实验探讨IFN-α通过IFN-α/IFNAR1/Jak-Stats途径刺激脐带MSCs表达TGF-β，上调SLE患者nTreg，抑制DCs产生IFN-α；并通过体外实验探讨脐带MSCs对SLE患者DCs的直接调控作用，深入阐明脐带MSCs与SLE内环境相互作用及直接/间接调控DCs的可能机制，为开展异体MSCs移植治疗SLE患者奠定理论基础。

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiorgan involvement. Allogeneic mesenchymal stem cells (MSCs) transplantation has become a new therapeutic option for SLE. We have demonstrated that type I interferon induced genes decreased after allogeneic MSCs transplantation in lupus patients. However, the underlying molecular mechanisms remain largely unclear and need to be further investigated. We have found that in vitro, IFN-α significantly stimulated MSCs to secret TGF-β and upregulated Treg. Thus, we hypothesize that IFN-α played a pivotal role in the MSCs mediated immunotolerance. In the current study, we will determine that in SLE patients, IFN-α stimulates MSCs to produce TGF-β via IFN-α/IFNAR1/Jak-Stats pathways, and then to upregulate nTreg, which inhibits DCs activity and IFN-α productions. On the other hand, MSCs can directly inhibit DCs to secret IFN-α. Here we will illustrate how allogeneic MSCs interact with lupus microenvironment and directly/indirectly modulate DCs activity. The conclusion of this study may provide further insight in understanding the mechanisms by which allogeneic MSCs effectively treat lupus patients.