Microglia undergo a series of phenotypic and functional changes during neuroinflammation11. Elevated expression of Cd83 was implied in the early activation of microglia, which was confirmed within this study. However, Cd83 expression not only coincides with early activation but is also elevated during chronic and remission disease phases. Other studies provided hints that CD83 is linked to cuprizone-induced demyelination52, ‘pre-activated’ human microglia12,22, and microglia from human white matter23. These data also suggest that CD83+ microglia play an important role in demyelinating diseases. Here, indeed, we show that prolonged CD83 expression is associated with a pro-resolving state of microglia. CD83-deficient microglia lapse into an over-active state, in which they attract inflammatory monocytes from the circulation and create a disease-promoting inflammatory environment. While CD83cKO cells are equally capable of phagocytosis, they react with altered expression of chemokines and gene transcripts involved in the degradation of lipids. Consequently, CD83 might not only mark activated cells but also be indicative of cells important for the clearance of debris and initiating the resolution of inflammation. Similarly, we have described that CD83-deficiency in DCs and macrophages
