IRF5 promotes inflammatory macrophage polarization and Th1/Th17 response
Résumé
Genetic polymorphisms in the IRF5 gene, leading to increased mRNA expression, are associated with a number of autoimmune diseases. We show that expression of IRF5 in macrophages is reversibly induced by inflammatory stimuli and contributes to plasticity of macrophage polarization. High levels of IRF5 are characteristic of M1 macrophages, in which it directly activates transcription of IL-12p40/p35, IL-23p19 genes and represses IL-10 gene. Consequently, these macrophages set up the environment for a potent TH1-TH17 response. Global gene expression analysis demonstrates that exogenous IRF5 up- or down-regulates expression of established phenotypic markers of M1 or M2 macrophages respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and defines a novel function for IRF5 as a transcriptional repressor.
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