Figure 6 Lack of IRF5 causes a reduction in neutrophil influx

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Figure 6 Lack of IRF5 causes a reduction in neutrophil influx and macrophage-derived CXCL1 in the arthritic knee Figure 6 | Lack of IRF5 causes a reduction in neutrophil influx and macrophage-derived CXCL1 in the arthritic knee. In a mouse model of antigen-induced arthritis, IRF5−/− mice display reduced knee swelling relative to wild-type (WT) mice, owing to a reduction in infiltrating neutrophils in the joint at early stages of disease. Macrophage numbers remain unaffected by loss of IRF5, but the proportions of MHCII+ proinflammatory macrophages decrease while the CD206+ population increases (relative to WT mice). Moreover, levels of the neutrophil chemoattractant CXCL1 are reduced in the absence of IRF5, overall and specifically in synovial macrophages. Ablation of IRF5 leads to a reduction in macrophage-secreted proinflammatory cytokines and an overall altered inflammatory environment in the joint. Consequently, disease severity is attenuated at later stages of the disease. Both the T-cell response in the knee and histological signs of membrane thickening and bone erosion are diminished in IRF5−/− mice. Udalova, I. A. et al. (2016) Macrophage heterogeneity in the context of rheumatoid arthritis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.91