Diterpenes drive Th1 polarization depending on IL-12

Sandaracopimaric acid and Sandaracopimaradiene-3β-ol are diterpenes isolated from the heatwood of Cryptomeria japonica and are pharmacologically active substances. Dendritic cells (DC) are key antigen presenting cells (APC), which link innate and adaptive immunity, ultimately activating antigen-specific T cells. We demonstrate that Sandaracopimaric acid and Sandaracopimaradiene-3β-ol activate humans DC as documented by phenotypic and functional maturation and altered cytokine production. The expression of the co-stimulatory molecules such as CD83, CD86 and HLA-DR on Sandaracopimaric acid- and Sandaracopimaradiene-3β-ol-primed DC was enhanced. Sandaracopimaric acid- and Sandaracopimaradiene-3β-ol-primed DC also enhanced the T cell stimulatory capacity in an allo MLR. Naive T cells co-cultured with Sandaracopimaric acid- or Sandaracopimaradiene-3β-ol-primed DC turned into typical Th1 cells, which produced large quantities of IFN-γ and released small amounts of IL-4 depending on IL-12 secretion. Sandaracopimaric acid- or Sandaracopimaradiene-3β-ol-primed DC had a high migration to macrophage inflammatory protein (MIP)-3β. These results suggest that some diterpenes modulate human DC function in a fashion that favors Th1 cell polarization and may be used on DC-based vaccines for cancer immunotherapy.