We also demonstrated that the regional expression pattern of Cd83 is retained under inflammatory conditions. Using a murine model for neuroinflammation, the EAE, we revealed that microglial expression of Cd83 increases especially in regions associated with white matter. While cortical regions are not severely affected, EAE-induced demyelination mainly pertains cerebellum, brainstem, and spinal cord50, where Cd83 expression strongly increases during EAE. Additionally, augmented Cd83 promoter activity coincides with cellular activation (i.e., CD11c+/MHC-II+ cells). This confirms recent data showing that during homeostasis, Cd83 is expressed in “pre-activated” or immune-alert microglial cells and that its expression increases in early phases of neuroinflammation11,26,27. In this respect, it is intriguing that Cd83 expression even proceeds when the cells re-acquire a less activated state, especially in spinal cord microglia. Spinal cord microglia have been demonstrated to exhibit a different gene expression pattern than cortical microglia, but these changes are mostly unaffected during EAE27,51. The prolonged expression of Cd83 in spinal cord microglia suggests that Cd83 is not only associated with acute activation but also with a reparative phenotype during the resolution phase of EAE. In line with this, Cd83 expression is detected in microglia after cuprizone-induced demyelination and remains elevated during remyelination52.
