Therefore, we propose that MPs could be the major source of circulating ICs in RA patients, which would lead to mononuclear phagocyte activation and the secretion of different mediators such as TNF-α, IL-6, and chemokines (CCL2, CCL3, and RANTES) that amplify the local and systemic inflammatory responses (Figure 4). Here, TNF is linked to rheumatoid arthritis.