Background/Purpose: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease, involving in dysfunction of many organs. The abnormality of apoptosis plays an important role in the pathogenesis of SLE. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have been confirmed to exert therapeutic effects on SLE. However, whether the benefit effects of UC-MSCs on SLE were mediated by regulating apoptosis remains to be elucidated. Mesenchymal stem cells (MSCs) have recently been used successfully in humans to control a lot of diseases. However, the mechanisms involved in their immunomodulatory effects remain a matter of debate. Here we explored whether lymphocytes apoptosis involved in the therapeutic effects of UC-MSCs in lupus mice.

Methods: One million human umbilical cord derived MSCs (UC-MSCs) were injected into B6.lpr mice via tail vein and 6 hours, 24 hours and four weeks later, all the mice were sacrificed, the apoptosis of lymphocyte in peripheral blood and spleen tissues as well as the expressions of Bim and Bcl-xl were detected by FACS, the immune cell subpopulations and cytokines in serum were also examined at 6 hours and 24 hours, respectively. The curative effects were assessed 4 weeks later.

Results:  UC-MSCs ameliorated disease progression of lupus mice, by regulating the percentage of immune cells, decreasing spleen weight and repairing kidney lesion. UC-MSCs promoted the lymphocyte apoptosis in peripheral blood and spleen tissues at 6 hours and 24 hours, reduced serum TGF-β1 levels, but did not affect Bim and Bcl-xl expressions in CD4+ and CD8+ T cells. Meanwhile, the percentage of Treg was significantly increased in MSCs transplantation group at both 6 and 24 hours. Reductions in the proportions of plasma cells, Th1,Th2 cells were also evident at 24 hours after MSCs infusion, while the levels of Tfh and Th17 cells had no significant change among different groups neither at 6 hours nor 24 hours.

Conclusion: MSCs may promote the apoptosis of T cells in lupus mice through regulating the immune cell subpopulation, decreasing total TGF-β1 in serum. Bim and Bcl-xl are not involved in it.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mesenchymal-stem-cells-ameliorate-lupus-by-promoting-t-cell-apoptosis-via-bcl-2bim-independent-pathway-in-mrllpr-mice/