New therapies and therapeutic targets – SLE

86 Mesenchymal stem cells induce lymphocytes apoptosis independent of bim and bcl-xl in lupus mice

Abstract

Background and aims 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 1^ 106 of human UC-MSCs were injected into B6.lpr mice via tail vein and 6, 24 hours and 4 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 and 24 hours, respectively. The curative effects were assessed 4 weeks later.

Results UC-MSCs ameliorated disease progression of lupus mice at 4 weeks, increasing the percentage of Treg while downregulating Tfh, plasma cells and Th1 cells, decreasing spleen weight and repairing kidney lesion. UC-MSCs promoted lymphocyte apoptosis in peripheral blood and spleen at 6 and 24 hours, and 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 the MSCT 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.

Conclusions UC-MSCs exhibit extensive pro-apoptosis properties against lymphocytes in B6.lpr mice, which may offer a form of immunomodulatory therapy for lupus.

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