Fig. 3: Regulatory mechanisms of KDMs in lymphocytes, NK cells, and macrophages differentiation.
From: Histone demethylases in the regulation of immunity and inflammation
The KDM6 subfamily is important for the development of T lymphocytes. KDM6A and KDM6B promote the expression of S1pr1 and Klf2, crucial for the maturation of T cells, by targeting promoter H3K27me3. Subsequently, KDM6B modifies the expression of Th17-related genes including Il22, Il17f, Il17, Rorγt, and Th1-related genes including T-bet and Smad3, promoting the differentiation into Th17 and Th1 cells, respectively. During the differentiation of B cells, KDM1A takes part in repressing PU.1, IRF4 and Blimp-1 through decreasing H3K4me3, which is crucial for the formation of plasmablasts. KDM5A recruited by p50 is responsible for the downregulation of Socs1 through erasing H3K4me3 in NK cells, inducing IFN production. In macrophages, KDM3C modulates H3K9me of the miR-302a promoter and inhibits M1 macrophage differentiation via the miR-302a/METTL3 axis. Finally, the KDM6B/IFR4 axis promotes the differentiation of M2 macrophages.
