along with Il1b, Nos2, Ptgs2, Arg1 and Nlrp3 (Fig. 4a, 4c), suggesting that decreased Spi1 expression may blunt the pro-inflammatory response of microglial cells to improve disease outcomes. Interestingly, expression of Cx3cr1 and Axl were elevated upon knock-down of Spi1 (Fig. 4c), raising the possibility that beneficial effects of changes in Spi1 expression are exerted through modulation of synaptic or neuronal clearance. Further experimental investigation of these phenotypes may shed light on the mechanisms of SPI1 modulation of AD risk. Of note, overexpression and knock-down of Spi1 in BV2 cells produce different and often opposite changes in expression of the genes profiled here, possibly driving alternative phenotypes that may underlie detrimental and protective roles of PU.1.
