タイトル； Epigenome reprogramming of M2 type macrophages by histone demethylase.
（熊本大学 発生医学研究所 細胞医学分野）
Macrophages are mainly categorized into two subsets, i.e. pro-inflammatory M1 type and anti-inflammatory M2 type. They showed distinct features such as cytokine profiles, and phagocytic activity, resulting in the regulation of immunity, angiogenesis, tissue repair, and tissue development. Although those functional differences between M1 and M2 macrophages are very important, the molecular mechanisms of M1/M2 polarization remain largely unknown. Here, in this study, we focused on the epigenetic regulation of macrophage polarization. We screened 770 epigenome modifying enzymes and found highly expressed 44 factors in human M2 macrophages. Among 44 factors, 3 genes were identified as highly expressed genes in mouse M2 macrophages in common. By using knockdown and knockout (KO) experiments, we found a histone demethylase KDM7 as a candidate gene. Kdm7 deficiency caused metabolic reprogramming upon M2 polarization. These data suggest a novel role of a histone demethylase Kdm7 in M2 polarization.