Since our data implied a role for CD83 in microglial activation, we next sought to investigate the impact of CD83 deletion on microglia. To this end, we crossed mice with floxed CD83-alleles to the tamoxifen-inducible CX3CR1-CreERT2 line (hereafter termed CD83ΔMG). Due to their long-lived nature, microglia are targeted by this approach even after short exposure to tamoxifen (Fig. 3a), and CD83 deletion was evident in microglia 7 weeks after initial tamoxifen treatment (Fig. 3b). It is well established that peripheral immune cells, such as DCs, are also targeted by CX3CR1-Cre mediated recombination, and we indeed observed a reduction of CD83+ splenic cDCs by approximately 50% 1 week after tamoxifen injection (Supplementary Fig. 3a). However, 7 weeks after tamoxifen treatment, when all further in vivo experiments commenced, splenic cDC populations have fully recovered CD83 expression, and bone-marrow-derived DCs from these CD83ΔMG animals also expressed similar levels of CD83 (Supplementary Fig. 3a, b). Thus, we confirmed the microglia-specific action of the inducible CD83cKO strategy. Since we observed that Cd83 regulation in microglia shares some characteristics with homeostatic genes, we first investigated the
