Interestingly, there is a conceivable overlap between the DAM gene signature and expression patterns observed in microglia that are associated with proliferation during CNS development or if CSF1R-signaling is disrupted13,14, suggesting common regulatory pathways. These datasets comprise several genes related to cellular activation, such as the Cd83 transcript. The corresponding glycoprotein was originally described as a maturation marker for dendritic cells (DCs) and is predominantly expressed in activated immune cells15. Recently, its immunomodulatory properties have become increasingly evident since CD83 expressed by DCs orchestrates their activation status and serves to restrain derailing immune responses16. CD83 expression in macrophages is part of an immediate-early response to inflammation17, and its deletion in those cells causes an impaired pro-resolving phenotype18. Thus, CD83 might exert similar regulatory functions during microglial activation. In the CNS, Cd83 expression is indeed largely confined to homeostatic murine microglia and border-associated macrophages19,20 and gets upregulated early during disease-associated transitions11,14,19,21. Furthermore, CD83 expression characterizes a specific ‘pre-activated’ set of human microglia that is reminiscent of DAMs, and it is also more prominent in microglia isolated from the white matter than
