Abstract
Research on regulation and its mechanism of bone marrow mesenchymal stem cells (BMSCs) on dendritic cells (DCs), which is the initiating factor in immune response has applicable clinical value. Although BMSCs have a significant regulatory effect on the maturation of DCs, its molecular mechanism is still unclear. BMSCs and DCs, were co-cultured by different concentration ratios. Flow cytometry was used to detect the expression of DC markers (CD83, CD11c). Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of related genes in RNA level. Expression of the target proteins was detected with using Western blot assay. miRNA inhibitor and miRNA mimic were used to suppress and up-regulate the expression of the target gene. In this research, our results demonstrated that BMSCs notably inhibited maturation of DCs in the co-culture system of BMSCs and DCs and confirmed that this inhibition is due to overexpression of miR-23b. Furthermore, this research found that miR-23b overexpression inhibited the expression of p50/p65, thus blocked the activation of the NF-κB pathway. In conclusion, BMSCs affected the activation of NF-κB pathway through miR-23b overexpression resulting in inhibition of the maturation and differentiation of DCs.
Highlights
Bone marrow mesenchymal stem cells (BMSCs) are multipotent non-haematopoietic adult stem cells, which are derived from the embryonic mesoderm
The obtained results of detecting dendritic cells (DCs) mature markers revealed that the co-cultured BMSCs with DCs has obvious inhibitory effect on the maturation of DCs compared with the cultured DCs alone; in the co-culture of DCs and BMSCs that transfected with miR-23b inhibitor, the maturation of DCs was not significantly inhibited (Figure 3A,C,D)
Some studies have found that immature DCs (iDCs) can promote the survival of cardiac allograft without the use of immunosuppressant [26]. iDCs inhibited the occurrence of acute graft compared with host disease (GVHD) after allogeneic bone marrow transplantation [27] and it can reduce the relapse of leukaemia [28]
Summary
Bone marrow mesenchymal stem cells (BMSCs) are multipotent non-haematopoietic adult stem cells, which are derived from the embryonic mesoderm. They can be highly self-renewable and have multidirectional differentiation potential. BMSCs have specific immunological properties, which can inhibit the proliferation and function of lymphocytes and suppress immunoreaction and induce immune tolerance [4]. BMSCs were co-cultured with CD19+ B cells and found that the proliferation of B cells was obviously inhibited [5]. BMSCs immune regulation is characterized by multiple pathways and mechanisms and mainly through two ways of secretion of immune regulatory factors and direct contact between cells. The immune regulation of BMSCs is a new hotspot in the field of transplantation, its specific mechanism is still unclear
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