As we have demonstrated, microglial expression of CD83 increases during neuroinflammation and is particularly high at the recovery phase of the EAE model (Fig. 2f, g). In addition, we have recently shown that CD83 expression in DCs restrains autoimmune inflammation in this model16. These data prompted the question whether CD83 deletion affects microglial function in the EAE model for neuroinflammation. To approach this issue, we immunized CD83ΔMG and CD83wtCre mice with MOG35–55 peptide to induce EAE and monitored disease progression over 30 days. When compared to control animals, CD83ΔMG mice showed exacerbated and prolonged paralytic symptoms, which is reflected in a significantly higher individual and cumulative disease score (Fig. 3e). To gain insight into the underlying processes, we isolated the CNS (i.e., brain and spinal cord) of EAE mice 18 days after immunization (peak of disease) and analyzed the phenotype and composition of immune cells (CD45+). Microglia from CD83wtCre EAE mice had significantly higher CD83 surface levels than those derived from CD83ΔMG mice (Supplementary Fig. 4a), thus confirming the KO efficiency. We also verified the KO-specificity in sorted microglia on
