The Role of Interferon Regulatory Factor 5 in Macrophage Inflammation During Osteoarthritis

Mounting evidence suggests that aberrant immune responses are involved in the pathogenesis of osteoarthritis (OA). Synovial macrophages are likely involved. In this study, we sought to investigate the role of interferon regulatory factor 5 (IRF5). In vitro M1-polarized macrophages presented significantly higher IRF5 expression than M2-polarized macrophages. Interestingly, IRF5 expression was observed in macrophages from the synovial fluid of OA patients, and the level of IRF expression was positively correlated with disease severity, such that stage 4 OA synovial macrophages presented significantly higher levels of IRF5 than stage 2 and stage 3 OA synovial macrophages. Circulating monocytes from OA patients, on the other hand, expressed little IRF5. However, synovial fluid from OA patients could significantly upregulate IRF5 expression in circulating monocytes. Synovial macrophages also expressed significantly higher IL-12 than circulating monocytes, and circulating monocytes conditioned in OA synovial fluid demonstrated significantly higher IL-12 expression. Direct IRF5 transfection could increase IL-12 expression in circulating monocytes. Interestingly, IRF5-transfected monocytes promoted the expression of Th1-associated genes in naive CD4 T cells via an IL-12-dependent mechanism. Overall, our study demonstrated that IRF5 expression was associated with OA severity and could contribute to the activation of the M1-Th1 axis.