系统性红斑狼疮(SLE)是一种常见的自身免疫病，异基因间充质干细胞(MSCs)移植治疗难治性SLE是一项新技术。前期动物实验已观察到狼疮鼠骨髓MSCs体外抑制B细胞活化增殖及分化的能力显著低于正常MSCs，但具体机制尚不清楚。我们发现狼疮鼠骨髓MSCs CCL2表达存在显著异常，且与其调控B细胞密切相关，推测狼疮MSCs调控B细胞异常可能与其CCL2表达减少有关。本课题拟进一步通过体内外实验探讨CCL2在MSCs调控B细胞中的关键作用，并通过临床及动物模型研究观察异基因MSCs移植对受体骨髓MSCs免疫调控功能的逆转作用，深入阐明异基因MSCs调节B细胞的分子基础及治疗SLE的具体机制。

Systemic lupus erythematosus (SLE) is an autoimmune disease.characterized by multiorgan involvement. Allogenic mesenchymal stem cells (MSCs).transplantation has become a new therapeutic option for refractory SLE. We have.demonstrated that bone marrow (BM) derived MSCs from MRL/lpr lupus mice were defective in inhibition on B cell activation, proliferation as well as differentiation when compared with those from normal controls. However, the underlying molecular mechanisms remain largely unclear and need to be further investigated. We have found that BMMSCs from lupus mice showed significant lower levels of CCL2 compared to normal BMMSCs, which was related to the defective function of MSC in regulating B cell maturation and antibody production in vitro. Thus, we.hypothesize that the abnormal regulation of B cells by MSCs from lupus mice may result from the dysregulated expression of CCL2. In the current study, we will determine a critical role of CCL2 in mediating B cell regulation by MSCs in vivo and in vitro. Moreover, both clinical studies and animal experiments will be conducted to confirm whether the immunomodulatory function of BMMSCs could be restored by allogenic MSCs.transplantation, which may provide further insight in understanding the mechanisms by which allogenic MSCs effectively treat lupus patients via modulating B cell functions.