Interestingly, microglia react with changes in Cd83 expression after stimulation in a unique manner: unlike other immune cells, microglia do not respond with elevated Cd83 expression after activation with pro-inflammatory mediators like LPS or TNF-α15. This regulation seems contradictive to the observed elevation of CD83 during EAE, but we provided evidence that CD83 expression during EAE is not only associated with activated microglia but rather even increases during the resolution phase. In line with this notion, alternative activation with IL-4 strongly induces Cd83 transcription in microglia, which has been also observed in bone-marrow-derived macrophages53. Interestingly, IL-4 acts differently on the microglial expression of Tmem119 and Cd83. Lentiviral CNS delivery of IL-4 induces microglial proliferation and a phenotype reminiscent of embryonic microglia54. Such proliferative region-associated microglia were shown to express less Tmem119 and more Cd83 (ref. 14; accessed via https://myeloidsc.appspot.com/), mirroring 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
