Proceedings of the National Academy of Sciences · 2009 · 705 citations · 33 references
Life SciencesImmunologyMolecular BiologyGene ExpressionInnate ImmunitySignal TransductionDendritic Cell BiologyInflammatory SignalingInnate Immune ResponseInnate Immune Signaling PathwaysMicrorna BiologyToll-like ReceptorsDendritic Cell Innate SensingDendritic Cell SignalingInflammatory Cytokine ProductionMicrorna In Immune RegulationNegative FeedbackNegative Feedback MechanismsToll-like Receptor SignalingToll-like Receptor Signaling Pathways
In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.
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