Macrophages, in response to different environmental cues, undergo the classical polarization (M1 macrophages) as well as the alternative polarization (M2 macrophages) that involve the functions of stimulus-specific transcription factors. Kruppel-like factor 4 (KLF4), a member of a subfamily of the zinc-finger class of DNA-binding transcription factors, plays as a critical regulator of macrophage polarization. KLF4 has been reported as a SUMOylated protein. In this study, we showed that SUMOylation of KLF4, is induced by IL-4 treatment in macrophages. IL4-induced KLF4 SUMOylation promotes RAW264.7 cells and bone marrow derived macrophages (BMDMs) to polarize into M2 subset. Thus, we identified an important post-translational modification (PTM), SUMOylation, plays a crucial role in regulating KLF4 activity during IL-4 induced macrophage M2 polarization. SUMOylation of KLF4 can be a potential therapeutic target in the resolution of inflammation.
Keywords: IL-4; Kruppel-like factor 4 (KLF4); SUMOylation; alternative polarization; macrophage.