TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ

Transforming growth factor (TGF)-beta 1 and mesenchymal stromal cells (MSCs) are two effective immunosuppressive agents for organ transplantation technology. This study aims to explore the molecular mechanism of TGF-beta 1-overexpressed MSCs on T cell immunosuppression. To achieve that, BM-MSCs were isolated from canine bone marrow, and their osteogenic differentiation and surface markers were detected. The TGF-beta 1 gene was transferred into lentivirus and modified MSCs (TGF-beta 1/MSCs) by lentivirus transfection. Furthermore, TGF-beta 1/MSCs were co-cultured with T cells to investigate their effect on differentiation and immune regulation. Results showed that TGF-beta 1/MSCs significantly downregulated the proportion of CD4(+) CD8(+) T cells in lymphocytes and significantly upregulated the proportion of CD4(+) CD25(+) T cells. Moreover, TGF-beta 1/MSCs significantly upregulated the expression of IL-10 in CD4(+) T cells and downregulated the expression of IL-17A, IL-21, and IL-22. Meanwhile, interferon-gamma (IFN-gamma) neutralizing antibody blocked the effects of TGF-beta 1/MSCs on the differentiation inhibition of Th17. Overall, our results confirm the strong immunosuppressive effect of TGF-beta 1/MSCs in vitro and demonstrate that IFN-gamma mediates the immunosuppressive effect of TGF-beta 1/MSC.

Automated summary

The study demonstrated the strong immunosuppressive effect of TGF-beta 1/MSCs in vitro, showing that they can lower the proportion of CD4(+) CD8(+) T cells and increase the proportion of CD4(+) CD25(+) T cells, while regulating the expression of IL-10, IL-17A, IL-21, and IL-22. The immunosuppressive effect of TGF-beta 1/MSCs is mediated by interferon-gamma (IFN-gamma).