摘要：SummaryDendritic cells (DCs) function is intimately linked to microenvironment and metabolism. Type I interferons (IFNs) condition dendritic cells to respond to weak self-signals, leading to autoimmunity. However, the metabolic adaption in the process is unclear. Here, we identified spermidine as a critical metabolite impacting the metabolic fitness of DC. First, dynamic metabolome screening indicated that spermidine decreased during IFN priming and following TLR7 ligand stimulation, accompanied by metabolic change from oxidative phosphorylation to glycolysis. Second, spermidine supplement restrained the glycolysis and prevented the overactivation of IFN-α primed DC bothin vivoandin vitro. Third, mechanism study uncovered that the activity of FOXO3 adapted to the metabolic change, mediating the anti-inflammatory effect of spermidine. More importantly, addition of spermidinein vivogreatly alleviated the development of psoriasis-like symptom in mice. Thus, our studies revealed metabolic changes boosting DC responses and identified spermidine as a potential therapeutic agent for autoimmune diseases.Graphical AbstractDisplay OmittedHighlights•Spermidine decreases in IFN-primed and TLR7 ligand-stimulated dendritic cells•Spermidine suppresses the activation of inflammatory dendritic cells•FOXO3 pathway mediates the function of spermidine•Spermidine supplement alleviated the development of psoriasis-like symptomBiological Sciences; Immunology; Cell Biology; Metabolomics
