Figure 1. Qualitative and quantitative differences in dendritic cell maturation affect T_H1/T_H2 polarization. Dendritic cell (DC) maturation can be initiated by various types of pattern recognition receptors, such as Toll-like receptors (TLRs), or by the receptors for various pro-inflammatory cytokines, such as the tumor necrosis factor α (TNFα) receptor TNFR. The genetic signatures resulting from TNFR-conveyed and weak TLR-conveyed signals are remarkably small and highly similar to each other, sharing a common pro-inflammatory component. When DC maturation is triggered by TNFR or weak TLR signals (TLR^low), the transcription factor NFκB can rapidly bind to the promoter region of genes coding for interleukin (IL)-1, IL-6 and TNFα. This type of DC maturation promotes T_H2-cell polarization. In response to these signals, no chromatin remodeling at the IL-12-coding gene promoter occurs to allow for the binding of NF-κB. In contrast, strong and prolonged TLR (TLR^high) signals are required to allow for chromatin remodeling at promoter region of the IL-12-coding gene and hence for the (delayed) binding of NFκB, resulting in the maturation of T_H1-polarizing DCs. This model integrates findings indicating that both DC maturation signal type (quality) and intensity (quantity) influence can T_H1 vs. T_H2-cell polarization.