Glycogen synthase kinase 3 activity during development of bone marrow-derived dendritic cells (DCs) essential for the DC function to induce T helper 2 polarization.

Dendritic cells (DCs) polarize naive CD4(+) T cells to either T helper 1 (Th1) or Th2 cells. We examined the role of glycogen synthase kinase 3 (GSK3) activity during DC development from murine bone marrow (BM) cells. DCs were generated by culturing lineage-marker-negative BM cells with granulocyte-macrophage colony-stimulating factor in the presence or absence of a specific inhibitor of GSK3 (Gi), SB415286, for 6 days. DCs generated in the presence (GiDC) or absence (control DC) of SB415286 similarly exhibited a conventional DC phenotype (CD11b(+) B220(-) CD8(-)). These DCs were mixed with allogeneic CD4(+) T cells and the ability to polarize Th1 or Th2 cells was evaluated. The GiDCs exhibited markedly impaired function to induce Th2 polarization compared to control DCs. In contrast, the ability of GiDCs to generate Th1 cells was slightly higher than that of control DCs. CD86 expression and CD40-mediated interleukin-6 production were completely diminished in GiDCs, which might be associated with the impaired ability of the GiDCs to induce Th2 differentiation. These results suggest that the GSK3 activity during DC development is essential for the establishment of the DC function to induce Th2, but not Th1, differentiation.