Interestingly, neutralization of both, IL-21 and IL-23 in RA CD4+ T cells not only yielded significant reduction in the expression of inflammatory cytokines TNF-α, IL-17 and IFN-γ, but also downregulated RANKL expression, directly indicating towards the critical role played by these cytokines in augmenting the inflammatory response as well as RANKL expression. This evidence concerns the gene TNF and rheumatoid arthritis.