Macrophages: A transcription factor to call their own

  • Minton K
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(IRF5) is a subset-defining factor for M1 macrophages with both activating and repressive transcriptional functions. Monocyte-derived macrophages that are differentiated with granulocyte–macrophage colony stimulating factor (GM-CSF) adopt an M1 (classical) phenotype, which is associated with the production of pro-inflammatory cytokines such as interleukin-12 (IL-12). Conversely, differentiation with M-CSF leads to the polarization of M2 (alternative) macrophages that produce anti-inflammatory cytokines such as IL-10. This study showed that treatment of human monocytes with GM-CSF but not M-CSF resulted in increased expression of IRF5. IRF5 was shown to bind to the promoter regions of the genes encoding IL-12p40, IL-12p35, IL-23p19 and IL-10. Recruitment of RNA polymerase II to the IL10 promoter only occurred after the dissociation of IRF5 from this region. This is in keeping with a role for IRF5 in transcriptional inhibition of the IL10 gene, and is supported by the demonstration that IRF5 inhibits the expression of a reporter construct containing the IL10 promoter sequence.

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  • Kirsty Minton

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