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

• Published in: Clinical transplantation Vol. 32; no. 4; pp. e13231 - n/a
• Main Authors: Hua, Fei, Chen, Yueqiu, Yang, Ziying, Teng, Xiaomei, Huang, Haoyue, Shen, Zhenya
• Format: Journal Article
• Language: English
• Published: Denmark 01.04.2018
• Subjects: allogeneic heart transplantation; bone marrow mesenchymal stem cell; CD4; CD8; dendritic cell; immune tolerance; allogeneic heart transplantation; CD4; immune tolerance; CD8; bone marrow mesenchymal stem cell; dendritic cell
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/ctr.13231

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‐γ 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‐γ, 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.