Allogenic mesenchymal stem cell transplantation ameliorates nephritis in lupus mice via inhibition of B-cell activation.

Abstract

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-β 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.

• Authors: Xiaolei Ma, Nan Che, Zhifeng Gu, Jing Huang, Dandan Wang, Jun Liang, Yayi Hou, Gary Gilkeson, Liwei Lu, Lingyun Sun
• Journal: Cell transplantation (Cell Transplant) Vol. 22 Issue 12 Pg. 2279-90 ( 2013) ISSN: 1555-3892 [Electronic] United States
• PMID: 23127285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• B-Cell Activating Factor
• Transforming Growth Factor beta
• Interleukin-10

Topics

• Animals
• Autoantibodies (immunology, metabolism)
• B-Cell Activating Factor (blood)
• B-Lymphocytes (immunology, metabolism)
• Bone Marrow Cells (cytology)
• Cells, Cultured
• Female
• Interleukin-10 (blood)
• Kidney (metabolism, pathology)
• Lymphocyte Activation
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred MRL lpr
• Nephritis (metabolism, pathology, surgery, therapy)
• Proteinuria (diagnosis)
• Spleen (metabolism, pathology)
• T-Lymphocytes (immunology, metabolism)
• Transforming Growth Factor beta (blood)
• Transplantation, Homologous