The study investigates the role of IRF5 in macrophage polarization and its impact on T cell responses. IRF5 is induced by inflammatory stimuli and is highly expressed in M1 macrophages, which are characterized by high levels of IL-12p40/p35, IL-23p19, and low levels of IL-10. IRF5 promotes the production of these cytokines and represses IL-10, leading to a potent T(H1-T(H17) response. Global gene expression analysis shows that IRF5 up-regulates or down-regulates the expression of M1 or M2 macrophage markers, respectively. IRF5 also inhibits the transcription of the IL-10 gene by directly binding to its promoter region. In a mouse model of M1 inflammation, *Irf5*^-/-^ mice exhibit reduced production of IL-12p40, IL-23p19, and TNF, and increased IL-10 levels. These findings suggest that IRF5 plays a critical role in M1 macrophage polarization and may be a potential therapeutic target for inflammatory diseases.The study investigates the role of IRF5 in macrophage polarization and its impact on T cell responses. IRF5 is induced by inflammatory stimuli and is highly expressed in M1 macrophages, which are characterized by high levels of IL-12p40/p35, IL-23p19, and low levels of IL-10. IRF5 promotes the production of these cytokines and represses IL-10, leading to a potent T(H1-T(H17) response. Global gene expression analysis shows that IRF5 up-regulates or down-regulates the expression of M1 or M2 macrophage markers, respectively. IRF5 also inhibits the transcription of the IL-10 gene by directly binding to its promoter region. In a mouse model of M1 inflammation, *Irf5*^-/-^ mice exhibit reduced production of IL-12p40, IL-23p19, and TNF, and increased IL-10 levels. These findings suggest that IRF5 plays a critical role in M1 macrophage polarization and may be a potential therapeutic target for inflammatory diseases.