We further noticed a clear trend that CD83-deficient microglia contributed more to the MHC-II+/Apoe+ cluster than control cells (Supplementary Fig. 5d). Therefore, we first assessed the activation status of CD83cKO microglia during EAE and detected significantly elevated proportions of activated (i.e., CD11c+/MHC-II+) microglia in the CNS of CD83ΔMG mice (Fig. 5a), paralleling the observed elevated proportion of monocyte-derived APCs in the CNS of these animals. Although MHC-II expression on microglia is regarded as dispensable for the EAE induction or perpetuation36, the CD11c/MHC-II double-positive phenotype is a typical hallmark of cellular activation during the disease28. Thus, CD83-deletion results in amplified activation, a notion that was further corroborated when we assessed the gene expression of microglia sorted from the CNS of EAE mice at the peak of the disease. The exaggerated activation was also reflected by significantly reduced mRNA levels of Tmem119 in microglia isolated from CD83ΔMG mice compared to controls (Fig. 5b). Microglia typically lose expression of signature genes such as Tmem119 during the transition from homeostatic to disease-associated phenotypes11,37. Interestingly, CD83-deficient microglia, despite being more activated, exhibited reduced surface levels
