SDF-1α Facilitates Mesenchymal Stem Cells to Induce Regulatory B Cell Differentiation from Patients with Immune Thrombocytopenia

Abstract

B cells play a central role in the pathogenesis of immune thrombocytopenia (ITP) by participating in humoral immunity. Meanwhile, regulatory B cells (Bregs), one subset of B cells, express negative regulatory effect on ITP. Mesenchymal stem cells (MSCs) have been demonstrated in the ability to induce immunosuppression, and stromal cell-derived factor-1α (SDF-1α) plays an important role in the migration and survival of MSCs. To investigate the mechanism of SDF-1α in controlling umbilical cord-derived MSCs (UC-MSCs) in inducing regulatory B cell differentiation of patients with ITP, we reconfirmed that SDF-1α promotes the proliferation of MSCs at the low doses of 0.05 μg/mL and 0.1 μg/mL but inhibits the proliferation and promotes the apoptosis of UC-MSCs at the high doses 0.5 μg/mL and 1 μg/mL; when UC-MSCs are cocultured with SDF-1α at 0.1 μg/mL, the decreased proportion of CD19+/CD24hi/CD38hi cells and IL-10-producing B cells (B 10 cell), considered as the Breg subset from ITP significantly enhanced, and the content of IL-10 in the supernatant is also obviously increased. The proportion of Bregs and the IL-10 secretion could be further promoted by the UC-MSCs treated with 0.1 μg/mL SDF-1α, which could also promote the miRNA-133 expression of UC-MSCs in an exosome-dependent manner; moreover, while the UC-MSCs were transfected with the miR-133 inhibitor, the proportion of induced Bregs decreased obviously when cocultured with peripheral blood mononuclear cells (PBMCs) of ITP. We conclude that UC-MSCs could effectively enhance the decreased proportion of Bregs from ITP; at appropriate concentrations, SDF-1α may promote the proliferating and survival ability of UC-MSCs and improve the production of Bregs induced by UC-MSCs through controlling miRNA-133 expression in the exosomes.