“…Consistent with the downregulation of IL-10 receptor signaling in Csf1r +/microglia, its downstream signaling mediator, Stat3 and several IL-10 transcriptional targets (Ddit4, Nfil3, Tsc22d3) (Ip et al, 2017, Lang et al, 2002, Berrebi et al, 2003, Hoppstadter et al, 2015 were also downregulated ( Fig 5B, F). Other potentially relevant downregulated genes encode transcripts associated with Alzheimer's disease (Sorl1) (Nicolas et al, 2016), leukodystrophy (Abcd1 and its downstream mediator of pathology, Ch25h) (Gong et al, 2017, Jang et al, 2016 and the CSF-2 target gene Pkch, encoding protein kinase Cη, a regulator of lipid metabolism and suppressor of NO production by macrophages (Torisu et al, 2016, Ozawa et al, 2016 ( Fig 5B). Pathway analysis revealed that the transcriptomic changes associated with Csf1r heterozygosity are consistent with activation of the RhoGDI signaling and LXR/RXR pathways ( Fig.…”