CSF-1R pTyr-721 controls expression of a specific subset of IEGs and DEGs associated with suppression of inflammation and promotion of an M2 phenotype. (A) Bar charts representing the relative abundance of a subset of pTyr-721–induced IEGs (left panel) and DEGs (center and right panels), illustrating pTyr-721–mediated decreased abundance of transcripts encoding proinflammatory (M1, *) molecules in conjunction with increased abundance of anti-inflammatory (M2, **) molecules. Known IEGs or DEGs are shown in bold. CSF-1–regulated transcript abundance in M−/−.WT cells (ie, log₂ fold change [FC] between the expression of the indicated RNA at the indicated time point and its measured expression at time 0) was normalized to CSF-1–regulated mRNA abundance in M−/−.Y721F macrophages calculated in the same manner. For a full set of pTyr-721–regulated genes, see supplemental Table 3. (B) Relative abundance of a subset of pTyr-721–induced genes in cells growing in CSF-1 (see supplemental Table 1) that encode secreted cytokines, illustrating the pTyr-721–mediated change in abundance of transcripts encoding M1 (*) and M2 (**) molecules (P < .05, FC > 1.5). (C-D) pTyr-721 suppresses secretion of proinflammatory molecules (*) and induces secretion of tumorigenic EGF, insulin-like growth factor-1 (IGF-1), and matrix metalloproteinase-3 (MMP-3). Conditioned medium from CSF-1–treated (120 ng/mL) and CSF-1–starved M−/−.WT and M−/−.Y721F macrophages was assayed for production of proinflammatory and proangiogenic factors using a mouse cytokine array permitting simultaneous measurements of 144 cytokines and soluble factors. For each cell line, signals detected for each cytokine produced by CSF-1–treated cells were integrated and normalized to the corresponding signal obtained from CSF-1–starved cells (duplicates ± range). (C) Molecules exhibiting pTyr-721–dependent increased secretion. (D) Molecules exhibiting increased secretion in the absence of pTyr-721 signaling. Error bars indicate the range of levels of biological duplicates.