Protective action of bone marrow mesenchymal stem cells in immune tolerance of allogeneic heart transplantation by regulating CD CD 45 RB RB + + dendritic cells

摘要

Abstract Background Bone marrow‐derived mesenchymal stem cells ( BMSC s) 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 BMSC s on immune tolerance of allogeneic heart transplantation and the involvement of CD 45 RB + dendritic cells ( DC s). Methods Bone marrow‐derived DC s and BMSC s were co‐cultured, with CD 45 RB expression on the surface of DC s 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 CD 4 + , CD 8 + , IL ‐2, IL ‐4, IL ‐10, IFN ‐γ were determined. Immunofluorescence assay was employed to determine intensity of C3d and C4d. Results DC s co‐cultured with BMSC s showed increased CD 45 RB and Foxp3 levels. CD 45 RB + DC s co‐cultured with T‐cells CD 4 + displayed increased T‐cell CD 4 + Foxp3 ratio and IL ‐10 than DC s. Both of them extended survival time of transplanted heart, decreased histopathological classification and score, intensity of C3d, C4d, proportion of CD 4 + , expression levels of IL ‐2 and IFN ‐γ, and increased the CD 4 + Foxp3 ratio and levels of IL ‐4 and IL ‐10. CD 45 RB + DC s achieved better protective effects than DC s. Conclusion BMSC s increased the expression of CD 45 RB in the bone marrow‐derived DC s, thereby strengthening immunosuppression capacity of T cells and immune tolerance of allogeneic heart transplantation.