TGF-β and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells

摘要: We previously demonstrated that agents known to signal infection or inflammation can rapidly and directly drive differentiation of human CD14+ monocytes into CD83+ dendritic cells (DCs) when introduced under serum-free conditions. In this study, we evaluated the effects TGF-beta vitamin D3 (VitD3) on proportion function adopt DC characteristics. significantly decreased adopted stable characteristics in response LPS, but had little no effect calcium ionophore-induced differentiation. contrast, VitD3 showed such pathway specificity dramatically suppressed DCs these agents. Both altered cytokine chemokine production LPS-treated monocytes, inhibited IL-12 IL-10 secretion, functional capacity DCs. Despite similar VitD3, there are significant differences signaling pathways used by agents, as evidenced their distinct LPS- differentiation, LPS-induced secretion IL-10, two members NF-kappaB family transcription factors, RelB cRel. These studies identify potent regulatory factors use suppress both well secrete Th1-polarizing IL-12. Because present serum negatively affect at physiological concentrations, our findings likely have significance regarding vivo role determining type immune responses.