PMA induces the differentiation of monocytes into immunosuppressive MDSCs

The induction of immune tolerance without the use of immunosuppressive drugs is a crucial problem in organ transplantation. The use of myeloid‐derived suppressor cells (MDSCs) as a cell‐based adjuvant immunosuppressive therapy is a bright clinical prospect in organ transplantation. MDSCs with stable immunosuppressive activities can be used to treat immune‐related diseases. In this study, macrophage colony‐stimulating factor (M‐CSF) was used to promote myeloid progenitor cell differentiation, and phorbol 12‐myristate 13‐acetate (PMA) was added to induce MDSCs at the later stage of induction in vitro . Cell phenotypes were detected by flow cytometry and mRNA was detected by real‐time–polymerase chain reaction (RT–PCR). A mouse skin transplantation model was used to investigate the cell inhibitory function. The combination of PMA and M‐CSF induced the differentiation of myeloid‐derived monocytes into MDSCs. MDSCs were found to induce immune tolerance by inhibiting the proliferation and activation of T cells, promoting cytokine secretion and inducing T cell transformation to regulatory T cells (T reg ). PMA significantly up‐regulated the expression of Arg‐1 and the Arg‐1 protein expression in MDSCs and arginase 1 (Arg‐1) inhibitor nor‐NOHA reversed the MDSC immunosuppressive activity, indicating the involvement of the Arg‐1 pathway in MDSC‐mediated immunosuppression. M‐CSF + PMA‐induced MDSCs also significantly prolonged the survival time of skin grafts in mice, showing that MDSCs exert immunosuppressive effects in vivo . We describe a novel scheme to induce immunosuppressive MDSCs in vitro . MDSCs induced by M‐CSF with PMA showed stable immunosuppression. MDSCs induced by this protocol may benefit patients with organ transplantation through immune regulation.