Curdlan Induces DC-Mediated Th17 Polarization via Jagged1 Activation in Human Dendritic Cells

ABSTRACTBackgroundTh17-inducing activity is carried by certain polysaccharides such as β-glucan derived from Candia albicans. Our previous studies have shown that Th1-and Th2-inducing activities can be qualitatively evaluated by the expression patterns of Notch ligand isoforms, using human monocyte-derived dendritic cells (Mo-DCs) and some leukemic cell lines such as THP-1. The association of Th17-inducing activities with Notch ligand expression patterns has been unclear.MethodsMo-DCs from healthy volunteers were co-cultured with HLA-DR-nonshared allogeneic CD4 + naive T cells to induce a mixed lymphocyte reaction, in the presence of adjuvants, such as curdlan. Culture supernatants were assayed for IFNγ, IL-5 and IL-17 by an enzyme-linked immunosorbent assay (ELISA). Notch ligand expression on Mo-DCs and THP-1 cells was evaluated by using RT-PCR.ResultsThe present study shows that curdlan, one of the β-glucans, has the ability to induce DC-mediated Th17 differentiation. It is also interesting to note that Jagged1 mRNA in Mo-DCs and THP-1 cells is up-regulated by curdlan. Furthermore, polyclonal anti-Jagged1 antibody inhibited such DC-mediated Th17 differentiation.ConclusionsThis study suggests that curdlan induces human DC-mediated Th17 polarization via Jagged1 activation in DCs.