Human Dendritic Cells Stimulated via TLR7 and/or TLR8 Induce the Sequential Production of Il-10, IFN-γ, and IL-17A by Naive CD4+ T Cells

摘要: Depending upon which TLRs are triggered, dendritic cells (DCs) may orient the differentiation of naive CD4 + T toward either Th1, Th2, regulatory cells, or recently defined Th17 lineage. In this study, we report that a dual stimulation TLR4 and TLR7/8 with LPS plus R848 leads human monocyte-derived DCs (MoDCs) to produce multiple pro- anti-inflammatory cytokines, including IL-10, IL-12, IL-23. Surprisingly, significant variability in up-regulation these cytokines is observed obtained from various healthy donors, approximately one three being “high responders.” High responding MoDCs stimulated via induce allogeneic cell secrete sequentially IL-10 IFN-γ, eventually IL-17A, whereas low only stimulate IFN-γ production. Both TLR7 TLR8 play central role phenomenon: triggering up-regulates expression on high responders, silencing mRNAs inhibits cytokine production R848-treated MoDCs, plasmacytoid constitutively expressing levels IL-17A by when alone. Collectively, our results illustrate synergy between controlling sequential proinflammatory cells. The polymorphism DC responses such TLR-mediated stimuli could explain differences susceptibility infectious pathogens autoimmune diseases within population.