Role of CCL2/CCR2 axis in the immunopathogenesis of rheumatoid arthritis: Latest evidence and therapeutic approaches

Evidence suggests that uncontrolled immune system responses and their components play a significant role in developing rheumatoid arthritis (RA), which is considered an autoimmune disease (AD). Among immune system mediators, cytokines and chemokines are involved in numerous physiological and pathological processes. CCL2 or monocyte chemoattractant protein-1 (MCP-1) is known as a CC chemokine that can induce the locomotion and recruitment of monocytes and macrophages to the site of injury. When CCL2 binds to its receptors, the most important of which is CCR2, various signaling pathways are triggered, eventually leading to various immunological events such as inflammation. This chemokine also participates in several events involved in RA pathogenesis, such as osteoclastogenesis, migration of effector T cells to the RA synovium tissue, and angiogenesis. In this review article, the role of the CCL2/CCR2 axis in RA pathogenesis and the immunotherapy opportunities based on CCL2/CCR2 axis targeting has been discussed based on existing investigations.