Recent single-cell transcriptomic analyses have suggested that CD83 is expressed in “pre-activated” or immune-alert microglial cells in homeostatic microglia and during early activation in a neuro-inflammatory context11,26,27. Since microglia rapidly respond when removed from their native environment5, we first assessed the regulation of CD83 on ex vivo cultivated cells. When we incubated acutely isolated adult microglia for 6 h at 37 °C, we observed a striking induction of surface CD83 expression. By contrast, cells, which were incubated at 4 °C for the same duration, showed no increased staining intensity compared to the background signal of CD83−/− microglia (Fig. 2a). Next, we immunized CD83-eGFP reporter mice with MOG35–55 peptide to induce experimental autoimmune encephalomyelitis (EAE), which models the early inflammatory phase of Multiple Sclerosis (MS) and assessed the expression of CD83 in microglia at the peak of disease. We disclosed not only a significant increase in eGFP-reporter activity but also elevated CD83 surface levels in microglia from inflamed CNS (Fig. 2b, c). It has been reported that activated microglia adopt a CD11c+/MHC-II+ phenotype during neuroinflammation28, and when we examined the phenotype
