期刊
CELL TRANSPLANTATION
卷 22, 期 12, 页码 2279-2290出版社
SAGE PUBLICATIONS INC
DOI: 10.3727/096368912X658692
关键词
Systemic lupus erythematosus; Mesenchymal stem cells; Transplantation; B-cell activating factor; B lymphocyte
资金
- Major International (Regional) Joint Research Projec [81120108021]
- National Natural Science Foundation of China [30972736]
- Jiangsu Province Natural Science Foundation [BK2009034]
- Jiangsu Province 'Six Summit Talent' Foundation, Jiangsu Kejiao Xingwei Program, and Nanjing Public Health Bureau Youth Startup Project [QYK11165]
Recent evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) possess immunosuppressive properties both in vitro and in vivo. We have previously demonstrated that transplantation of human MSCs can significantly improve the autoimmune conditions in MRL/lpr mice. The current study aimed to determine the mechanisms by which murine BM-MSC transplantation (MSCT) ameliorates nephritis in MRL/lpr mice. In this study, we found that MSCT can significantly prolong the survival of MRL/lpr mice. Eight weeks after transplantation, MSCT-treated mice showed significantly smaller spleens than control animals, with fewer marginal zones (MZs), T1, T2, activated B-cells, and plasma cells. Moreover, serum levels of B-cell activating factor (BAFF) and IL-10 in MSCT-treated mice decreased significantly compared to those in the control group, while levels of serum TGF-beta were increased. Notably, decreased BAFF expression in both spleen and kidney was accompanied by decreased production of anti-dsDNA autoantibodies and proteinuria in MSCT-treated mice. Since BAFF is mainly expressed by T-cells and dendritic cells, we incubated BM-MSCs and DCs together and found that the production of BAFF by DCs was suppressed by MSCs. Thus, our findings suggest that MSCT may suppress the excessive activation of B-cells via inhibition of BAFF production in MRL/lpr mice.
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