| First Author | Li G | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 1 | Pages | 100807 |
| PubMed ID | 31962236 | Mgi Jnum | J:333221 |
| Mgi Id | MGI:6717604 | Doi | 10.1016/j.isci.2019.100807 |
| Citation | Li G, et al. (2020) Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity. iScience 23(1):100807 |
| abstractText | Dendritic 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-alpha primed DC both in vivo and in 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 spermidine in vivo greatly 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. |
