Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD45RB+ dendritic cells

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect and therefore may have a therapeutic potential in T-cell-dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB(+) dendritic cells (DCs). Methods: Bone marrow-derived DCs and BMSCs were co-cultured, with CD45RB expression on the surface of DCs measured by flow cytometry. qRT-PCR and Western blotting were used to detect mRNA and protein levels. Cytometric bead array was performed to determine the serum level of IL-10. Survival time of transplanted heart and expression of CD4(+), CD8(+), IL-2, IL-4, IL-10, IFN-gamma were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results: DCs co-cultured with BMSCs showed increased CD45RB and Foxp3 levels. CD45RB(+) DCs co-cultured with T-cells CD4(+) displayed increased T-cell CD4(+) Foxp3 ratio and IL-10 than DCs. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD4(+), expression levels of IL-2 and IFN-gamma, and increased the CD4(+) Foxp3 ratio and levels of IL-4 and IL-10. CD45RB(+) DCs achieved better protective effects than DCs. Conclusion: BMSCs increased the expression of CD45RB in the bone marrow-derived DCs, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.