Taken together, this suggested that IL-21 and IL-23 were responsible for modulation of inflammatory cytokines, IL-17, TNF-α, IFN-γ as well as RANKL, thus establishing and validating our hypothesis; IL-21/IL-23 axis dictates the pathways regulating inflammation and RANKL expression in aberrant CD4+ T cells in RA. This evidence concerns the gene IFNG and rheumatoid arthritis.