Transplantation of mesenchymal stem cells ameliorates systemic lupus erythematosus and upregulates B10 cells through TGF-β1

BACKGROUND: Considerable experimental and clinical evidences have proved that human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation was powerful in systemic lupus erythematosus (SLE) treatment. MSCs could upregulate regulatory B cells (Bregs) in the mice model of the other immune disease. However, the regulation of MSCs on Bregs in SLE environment remains unclear. METHODS: To assess the abilities of UC-MSCs to treat SLE, MSCs were transferred intravenously to 17- to 18-week-old MRL/lpr mice. Four weeks later, mice were sacrificed. Survival rates, anti-dsDNA antibodies and renal histology were evaluated. CD4(+) T helper (Th) cell subgroups and interleukin (IL)-10(+) Bregs (B10) in the spleen were quantitated by flow cytometry. The changes of transforming growth factor (TGF)-β1, IL-6 and indoleamine 2,3-dioxyenase (IDO) mRNAs expressed by MSCs after co-cultured with B cells were detected using real-time polymerase chain reaction (RT-PCR). MSCs were infected by lentivirus carrying TGF-β1 shRNAs, then MSCs with low expression of TGF-β1 were conducted for co-culture in vitro and transplantation experiments in vivo. RESULTS: UC-MSCs transplantation could efficiently downregulate 24 h proteinuria and anti-dsDNA antibodies, correct Treg/Th17/Th1 imbalances and increase the frequency of B10 cells. The expression of TGF-β1 in MSCs was significantly increased after co-culture with B cells. Downregulation of TGF-β1 in MSCs could significantly attenuate the upregulation of B10 by MSCs in vitro and in vivo. Downregulation of TGF-β1 also compromised the immunomodulation effects of MSCs on Th17 and Treg cells and the therapeutic effects of MSC transplantation. CONCLUSIONS: UC-MSCs could protect against SLE in mice and upregulate IL-10(+) Bregs via TGF-β1.