Berberine Suppresses Th17 and Dendritic Cell Responses

PURPOSE. Berberine (BBR) has been shown to exert immunosuppressive and anti-inflammatory effects in several autoimmune diseases. This study was designed to investigate the possible effect of BBR on Th17 and dendritic cell (DC) responses. METHODS. Twelve patients with active VKH disease and 20 healthy individuals were enrolled in this study. CD4(+) T cells and CD14(+) monocytes were isolated from peripheral blood mononuclear cells using magnetic-activated cell sorting. Monocyte-derived DCs were generated by culturing monocytes with GM-CSF and IL-4. Proinflammatory cytokines secreted by CD4(+) T cells and LPS induced DCs when exposed to BBR or only vehicle were detected by ELISA. The frequency of IL-17-producing CD4(+) T cells and the surface markers of BBR-treated DCs were measured by flow cytometry. RESULTS. Activation of CD4(+) T cells using anti-CD3 and anti-CD28 showed a higher Th17 response in active VKH patients. BBR showed a direct suppression of the Th17 response both in active VKH patients and healthy donors. It also suppressed the Th17 response indirectly by influencing DC maturation. On the one hand, BBR downregulated the expression of costimulatory molecules (CD40, CD80, and CD86) and, on the other hand, it inhibited IL-6, IL-1 beta, and IL-23 secretion by DCs. CONCLUSIONS. These findings suggest that the inhibitory effect of BBR on the Th17 response was mediated by a direct action on T cells as well as an indirect effect via DCs. This study provides new evidence that the natural compound BBR is of great value in the search for novel therapeutic agents in the treatment of T-cell-mediated autoimmune diseases.