Our studies significantly expand knowledge of the expression changes in epigenetic regulators during polarization of human macrophages. Upregulation or downregulation of genes does not necessarily imply that these will be the only enzymes that play a major role in responses to IFN-γ or IL-4. However, the previous literature on CIITA and NCOA1 together with our new results with KDM6B illustrates the importance of upregulated genes. Importantly, we identify several changes that are independent of inhibition of proliferation, a complicating factor that appears to have been overlooked in previous studies. However, those changes partly dependent of proliferation may also be of significance. Indeed, recent work has highlighted the importance of proliferation in replenishing populations of resident macrophages (79). There have also been interesting findings in models of inflammation, especially atherosclerotic plaque formation (80), suggesting that proliferation rather than recruitment may play the major role in sustaining macrophage numbers. From our data, proliferation has a major impact on epigenetic programing, and this undoubtedly influences macrophage behavior. Future work, beyond the present scope, should probe into the downregulated genes we have identified, many of which are virtually unstudied in macrophages. However, we recognize that mechanisms other than changes in expression level regulate the function of epigenetic writers, readers and erasers at the promoters and enhancers of pro- and anti-inflammatory genes (61, 81). Except in the case of KDM6B, the contribution that the expression changes we observed make to epigenetic regulation in macrophages remains to be established.