Unique Response Of The Differentiated Dendritic Cells (diffDC) To LPS Stimulation/TLR4 Signaling And The Related Mechanisms

We report here the unique response of the differentiated dendritic cells (diffDC) to LPS stimulation/TLR4 signaling and the related mechanisms. We investigated the cytokines and chemokine IP-10 expression patterns of this new regulatory DC subset after stimulation with or without LPS, and then went further to analyze which signal pathway involved in the unique response of the diffDC to LPS stimulation, resulting in high IL-10, IP-10 and low IL-12 production. our data suggest that diffDC secrete significantly higher levels of IL-10 and NO but lower levels of IL-12p70 as compared with maDC, and the increased IL-10 and NO production by diffDCs more profounded after LPS stimulation. p38 is poorly phosphorylated and ERK1/2 can be significantly activated in diffDC. Superactivation of ERK in diffDC is involved in the higher IL-10 production by diffDC. Interestingly, diffDC secrete high level of IP-10 through the increased production of IFN-β by activating STAT1.Therefore, the unique expression pattern of cytokines and chemokines by diffDC may help diffDC to exert their special and powerful regulation of inflammation and immune responses, thus playing an important role in maintaining immune homeostasis.