IRF5 promotes inflammatory macrophage polarization and Th1/Th17 response. The study shows that IRF5 is highly expressed in M1 macrophages and contributes to their polarization. IRF5 activates the transcription of IL-12p40/p35 and IL-23p19 genes, while repressing the IL-10 gene. This leads to a pro-inflammatory environment that supports a potent Th1-Th17 response. IRF5 also influences the expression of M1 and M2 macrophage markers, suggesting a critical role in macrophage polarization. The study also demonstrates that IRF5 directly induces the transcription of M1-specific genes and inhibits the transcription of the IL-10 gene. In mouse models, IRF5 deficiency leads to reduced production of M1-specific cytokines and increased IL-10, highlighting its role in establishing a pro-inflammatory macrophage phenotype. The findings suggest that IRF5 plays a key role in macrophage polarization and that its regulation could be a target for therapeutic interventions. The study also highlights the importance of IRF5 in the immune response, particularly in the context of inflammation and autoimmune diseases.IRF5 promotes inflammatory macrophage polarization and Th1/Th17 response. The study shows that IRF5 is highly expressed in M1 macrophages and contributes to their polarization. IRF5 activates the transcription of IL-12p40/p35 and IL-23p19 genes, while repressing the IL-10 gene. This leads to a pro-inflammatory environment that supports a potent Th1-Th17 response. IRF5 also influences the expression of M1 and M2 macrophage markers, suggesting a critical role in macrophage polarization. The study also demonstrates that IRF5 directly induces the transcription of M1-specific genes and inhibits the transcription of the IL-10 gene. In mouse models, IRF5 deficiency leads to reduced production of M1-specific cytokines and increased IL-10, highlighting its role in establishing a pro-inflammatory macrophage phenotype. The findings suggest that IRF5 plays a key role in macrophage polarization and that its regulation could be a target for therapeutic interventions. The study also highlights the importance of IRF5 in the immune response, particularly in the context of inflammation and autoimmune diseases.