the results obtained with IL-4 treatment of our in vitro cultures. In addition, alternatively activated microglia serve to induce oligodendrocyte differentiation during remyelination46,55, suggesting a pro-resolving function of CD83+ microglia. This connection is further substantiated by the fact that we observed less Lpl expression in CD83-deficient microglia from either healthy or EAE mice since Lpl expression is also associated with an alternatively activated phenotype56. Additionally, Lpl-deficient microglia have been shown to accumulate excessive amounts of lipid droplets, which deteriorates microglial function and induces a pro-inflammatory transcriptional program42,57. We also detected less Trem2 expression in CD83-deficient microglia both in the steady state and under inflammatory conditions. Trem2-KO mice show a defective response to myelin debris in the cuprizone demyelination model and are incapable of inducing Lpl expression, amongst other transcripts involved in lipid metabolism58. Interestingly, another study on Trem2-KO mice has reported that microglia from these mice express less Cd8359. This implies an important regulatory circuit between CD83, Trem2, and Lpl in microglia, which are challenged with myelin debris, for instance, after neuroinflammation-induced demyelination. By performing scRNA-Seq analyses, we discovered a microglial cell cluster that expressed particularly high levels of Cd83 (Ccl4+ cluster, see Fig. 4d, e). This cluster not only
