All-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway.

BACKGROUND: All-trans retinoic acid (ATRA) potentiates TGF-β-dependent regulatory T cells (Treg) induction, while it inhibits pro-inflammatory interleukin-17-producing T helper cells (Th17) differentiation. Combined application of ATRA and TGF-β may shift Treg-Th17 balance towards Treg.

OBJECTIVE: To investigates the effect of ATRA on the regulation of Th17-Treg balance through ERK and p38 signaling pathway.

METHODS: Mice naive CD4+T cells were isolated and co-cultured with 100 nmol/ml ATRA and 5 ng/ml TGF-β. The effect of ATRA on the phosphorylation of ERK and P38 was evaluated. The induction of Treg and Th17 was investigated before and after the application of the inhibitor of ERK and P38.

RESULTS: The expression of p-ERK1 and p-ERK2 increased significantly when the cells were incubated for 3 days with both TGF-β and ATRA. The upregulated expression of p38 was found after incubation for 1 day. The inhibition of ERK prohibited Treg induction and promoted Th17 development. However, the inhibition of p38 only had inhibitory effect on Treg induction.

CONCLUSIONS: ERK and p38 pathways participated in ATRA-activated Treg-Th17 balance adjustment.