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 expression of such genes in microglia from CD83ΔMG mice. We detected a clear but not significant trend toward less expression of Tmem119 and especially Siglech in CD83-deficient microglia (Supplementary Fig. 3c), while transcripts of Entpd1, encoding the ectonucleotidase CD39, were significantly reduced (Fig. 3c). Since loss of homeostatic gene expression often coincides with acquisition of a DAM phenotype32,33, we next investigated the expression of important DAM-genes in CD83-deficent microglia. Surprisingly though, expression levels of DAM-genes Trem2 and Lpl were significantly reduced in CD83-deficient cells while DAM-associated scavenger receptors, such as Msr1 or Clec7a, were unaffected (Fig. 3d, Supplementary Fig. 3d). The same applied for Apoe, which cooperates with TREM2 signaling in promoting the DAM phenotype (Supplementary Fig. 3d).
