Regulatory effect of rat bone marrow mesenchymal stem cells on Treg/Th17 immune balance in vitro

Bone marrow mesenchymal stem cells (BM‑MSCs) regulate the balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells. However, the role of different factors on BM‑MSCs‑mediated regulation of the Treg/Th17 balance is unknown. BM‑MSCs and CD4+ T lymphocytes were co‑cultured with various treatments. The ratio of Treg/Th17 cells was calculated and the expression of different cytokines was measured. BM‑MSCs were found to have a proliferative effect on Th17 cells at a basal concentration and at a 2‑fold increase in the number of BM‑MSCs. However, when the number of BM‑MSCs used was increased 4‑fold, they had an inhibitory effect on the Th17 cells. The effect of BM‑MSCs on Tregs was inhibited by the addition of tacrolimus but not rapamycin. The effect of BM‑MSCs on Th17 cells was inhibited by rapamycin. Additionally, the effect of BM‑MSCs on Tregs were inhibited by the addition of a transforming growth factor‑β (TGF‑β) blocker, whereas these TGF‑β‑blockers had no effect on Th17 cells. Addition of an interleukin (IL)‑2 blocker reduced the proportion of Th17 cells when co‑cultured with a high number of MSCs compared with the low concentration group and the proportion of Treg cells was significantly decreased when cells were treated with an IL‑2 blocker compared with the control group. Together, these results showed the varying effects of MSCs on the ratio of Treg/Th17, its dependence on the number of MSCs and the effects of cytokines in inducing these changes in the balance.