Microglia are undisputed central players in neuronal immune processes. They fulfill a plethora of tasks during CNS homeostasis but also critically affect the course of neurologic disorders like neurodegeneration and neuroinflammation48. In this study, we disclosed that the CD83 molecule acts as a regulatory node governing microglial activation during neuroinflammation. We also provide evidence that physiological Cd83 expression in microglia is subject to regional heterogeneity with the highest expression levels in the spinal cord, which is in line with previously published single-cell data27. Interestingly, those regions with higher Cd83 expression consist mainly of white matter. In human microglia, CD83 expression is particularly high in cells from white matter versus gray matter23, a finding which we confirmed on the protein level (see Fig. 1e). Interestingly, we observed an association of CD83 with a rather ameboid cell shape, indicative of activation. Human white matter microglia show elevated activity of the NF-κB pathway, which subsequently could activate CD83 transcription via specific binding sites present in the CD83 promoter23,49.
