DRP008564
Myeloid-derived suppressor cells induced by combination treatment of FTY720 plus pathogenic antigen has high suppressive potential
Combination treatment with fingolimod (FTY720) and pathogenic antigen prevent progression of glucose-6-phosphate isomerase (GPI)325-339-induced arthritis. In this study, we focused on myeloid-derived suppressor cells (MDSC; CD11b+Gr-1+ cells) and investigated the effects of combination treatment on the cells. GPI325-339-induced arthritis in DBA/1J mice was treated with FTY720 and/or GPI325-339 for five days. The percentage of CD369+CD11b+Gr-1+ cells effectively increased in combination-treated mice. The inhibitory potential of CD369+CD11b+Gr-1+ cells was higher than that of cells not expressing CD369. From experiments using bone marrow cells, it was found that in CD11b+Gr-1+ cells, the expression of CD369 was increased by stimulation with granulocyte-macrophage colony-stimulating factor, and the expression of CD11c was increases accordingly. The increased expression of CD11c was found to mean a decrease in the potential to suppress T cell proliferation from the results of the suppression assay. The percentage of CD11c-CD369+ cells in the CD11b+Gr-1+ cells that induced by the combination treatment increased. In conclusion, it was considered that the combination treatment of FTY720 and pathogenic antigen effective induces MDSC, which has high potential to suppress T cell proliferation in the lymph nodes, thereby constructing an immune tolerant state.