Polyacetylenediols regulate the function of human monocyte-derived dendritic cells

Abstract

Callyspongidiol and 14,15-dihydrosiphonodiol are Polyacetylenediols isolated from marine sponges and are pharmacologically active substances. Dendritic cells (DC) play an important role in the initiation and regulation of immune response. DC have a key influence in the differentiation of naïve T cells into Th1, Th2 or Th17 effector cells. We demonstrated that callyspongidiol and 14,15-dihydrosiphonodiol activate human DC as documented by phenotypic and functional maturation, and altered cytokine production. Up regulation of cell surface expression of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 was observed following DC treatment with callyspongidiol and 14,15-dihydrosiphonodiol. The production of IL-10 by callyspongidiol-primed DC after stimulation with CD40-L was higher than that of LPS- or 14,15-dihydrosiphonodiol-primed DC. Naïve T cells co-cultured with allogeneic 14,15-dihydrosiphonodiol-primed DC at 1:5 DC/T cell ratio turned into typical Th1 cells depending on IL-12 secretion and independent on TLR2 or TLR4. In contrast, callyspongidiol-primed DC co-cultured with naïve T cells secreted IL-4 and IL-10, but had little effect on IFN-γ. Callyspongidiol-primed DC induced the development of Th2 cells via the inhibition of IL-12p70 and the enhancement of IL-10. Polyacetylenediols-primed DC expressed the chemokine receptor CCR7 and had a high migration to CCL19. These results suggested that some Polyacetylenediols modulate human DC function in a fashion that favors Th1/Th2 cell polarization or IL-10 producing T cells, and might have implication in tumor or in autoimmune diseases.