The Role of TNF-α in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) induces articular damage through autoimmunity. Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of RA. TNF-α binds to its receptors to recruit certain molecules and forms two kinds of complexes (complex Ⅰ and Ⅱ) to regulate the pro-survival, apoptosis, and necrosis of cells. TNF-α upregulates RA by the methylation and acetylation of the RA synovial fibroblast gene and causes RA-derived joint damage through the induction of osteoclasts. Two TNF-α receptors mediate RA in opposite directions. TNF-α has been a target for the treatment of RA in which TNF-α inhibitors (TNFi) are administrated periodically for RA patients. Several mechanisms in the RA-related TNF-α signaling pathways remain imprecise including the regulation of regulatory T cells, osteoclast induction, and the potential interaction with the hypoxia-inducible factor. Further investigation into these questions may point out new methods for RA treatment to overcome the defects of current TNFi such as the anti-drug antibodies.