We chose to prioritize the lysine demethylase, KDM6B, for study in greater detail because it removes repressive H3K27Me3 marks and is, therefore, a putative transcriptional activator. It is also amenable to selective pharmacological inhibition, which would lead to downregulation of target gene expression. Furthermore, KDM6B has been previously implicated in macrophage polarization by either bacterial LPS or IL-4, depending on the source of macrophages investigated. For example, KDM6B is upregulated in response to bacterial LPS in both mouse (78) and human (39) macrophages; and as many as 70% of LPS responsive genes in mouse macrophages recruit KDM6B to their promoters (15). This does not always lead to H3K27 demethylation (15) but KDM6A and B nevertheless act redundantly to potentiate responses to LPS in human macrophages (39). Other work in mouse macrophages showed that KDM6B can be upregulated by IL-4 in a STAT-6-dependent manner and that it is essential for IL-4 induced polarization in vitro and in response to certain kinds of parasitic infection in vivo (14, 17). However, no previous study has investigated the role of KDM6B on both pro-inflammatory and anti-inflammatory polarization in the same preparation of macrophages. Our transcriptomic study demonstrated for the first time that KDM6A and B play a part in polarization by IFN-γ, although a smaller proportion of genes (approximately 20%) appear to be affected than for responses to LPS (39). Likewise, KDM6B modulates some IL-4 polarization genes alone or redundantly with KDM6A in human macrophages but this seems to be a much small proportion (11%) than in mouse macrophages (14, 17). The finding that KDM6A and B acted redundantly for some processes is consistent with the previous study on LPS (39).