English

Abstract

Introduction Rheumatoid arthritis is caused by a complex mechanism involving synoviocytes, osteoclasts and immune cells that are interconnected via cytokines and other signalling molecules. Effective medical treatment for joint destruction in rheumatoid arthritis is lacking because the molecular mechanisms leading to joint destruction are incompletely understood. However, it is known that cytokinemediated immunity and perturbations in the balance of effector cells at the disease site play a crucial role in rheumatoid arthritis pathogenesis. Cellular and cytokine inhibitors have been used for treatment purposes. Increasing evidence has revealed the importance of IL-17, an activated T cell-derived inflammatory cytokine, and IL-23 in the pathogenesis of rheumatoid arthritis. The role of IL-17 has been of particular interest, as IL-17 affects the differentiation and activation of pathogenic osteoclasts. Cellularly, the key features of rheumatoid arthritis include disturbance of the Th17/Treg balance and plasticity, deregulated Th17 responses and the reduction or absences of Treg cells. Recent developments in the area of CD4 + T-cell differentiation, together with experimental and preclinical findings on inhibitors of the IL-17 pathway and the use of Treg cell-based therapy, indicate that CD4 + effector cells, TH17 and Treg, could be effective targets for restoring immune tolerance. In this critical review, we summarise the progress in our understanding of the role of IL-23, IL-17 and CD4 + T-cell differentiation into specialised effectors, focusing on Th17 and Treg cells, in the pathogenesis of rheumatoid arthritis. Conclusion Pathogenesis of rheumatoid arthritis is slow and complex. Cytokines and cell-mediated immunity are involved in irreversible bone and cartilage destruction. Cytokine levels and the Treg/Th17 balance might be relevant for the diversity of clinical manifestations in rheumatoid arthritis patients and might be critical for the development of improved treatment methods.