Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

Figure 6 IMT504 effects on the immune system. Primary targets of IMT504 are B lymphocytes (B), PDCs, NK and NKT cells. IMT504 acting on B and PDCs induces a phenotype of antigen presenting cells, which in the presence of an appropriate antigenic stimulus initiates a strong adaptive immune response[371-373]. On the other hand, IMT504 acting on NK and NKT cells, in collaboration with IL-2, induces the strong secretion of IFN-γ and TNF-α that can induce MSC immunosuppressive properties and of GM-CSF that can activate MDSCs. This immunosuppressive pathway is inhibited by the presence of IFN-α. Reciprocally, IMT504 inhibits IFN-α secretion by PDCs. Therefore, activation of this immunosuppressive pathway depends on the balance between IMT504 activity and activity of IFN-α inducers that are present[331]. PDCs: Plasmacytoid dendritic cells; NK: Natural killer; NKT: Natural killer T; IL-2: Interleukin-2; IFN-γ: Interferon-gamma; TNF-α: Tumor necrosis factor-alpha; GM-CSF: Granulocyte macrophage colony-stimulating factor; MDSCs: Myeloid-derived suppressor cells.