After being activated, microglia in the central nervous system (CNS) fail to acquire an anti-inflammatory phenotype, and bone marrow–derived monocytes must be recruited for resolution of the microglia-induced inflammation. In The EMBO Journal, Cohen et al. show that extended exposure to the cytokine TGF-β impairs the conversion of proinflammatory (M1) macrophages into anti-inflammatory (M2) macrophages by dampening the expression of the transcription factor IRF7. Preexposure to TGF-β, which is highly expressed in the CNS, prevents induction of the M2 phenotype during the late-stage response to lipopolysaccharide in microglia or bone marrow–derived macrophages and downregulates expression of interleukin 10 (IL-10) and the transcription factor IRF7, a profile that is also found ex vivo in microglia isolated from the CNS. Stimulation with interferon-β, a known inducer of IRF7, allows M1-to-M2 conversion in TGF-β-exposed microglia in vitro and in vivo. Thus, tissue-specific environmental factors have an essential role in the fate of resident macrophages.
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Visan, I. Too much of a good thing. Nat Immunol 16, 12 (2015). https://doi.org/10.1038/ni.3070
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DOI: https://doi.org/10.1038/ni.3070
