Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization [Immunology]

January 2nd, 2014 by Date, D., Das, R., Narla, G., Simon, D. I., Jain, M. K., Mahabeleshwar, G. H.

Accumulating evidence supports the importance of macrophage plasticity in a broad spectrum of biological processes operative in health and disease. A major locus of control regulating macrophage polarization is at the transcriptional level and several major pathways have been elucidated in recent years. In this study, we identify the Kruppel-like transcription factor 6 (KLF6) as a molecular toggle controlling macrophage speciation. KLF6 expression was robustly induced by pro-inflammatory M1 stimuli (e.g. LPS, IFN-g) and strongly suppressed by M2 stimuli (e.g. IL4, IL-13) in human and murine macrophages. Gain- and loss-of-function studies suggest that KLF6 is required for optimal LPS-induced pro-inflammatory gene expression, acting cooperatively with NF-kB. Further, KLF6 inhibits anti-inflammatory gene expression by negatively regulating PPARg expression in macrophages. Collectively, these observations identify KLF6 as a novel transcriptional regulator of macrophage polarization.