Most of the existing evidence indicates that synovial NK cells exert pathogenic effects in RA by directly promoting cell or tissue injury either by inducing cytotoxicity (e.g., in synovial fibroblasts) expressing activating ligands for NK cell receptors or by secreting inflammatory cytokines (e.g., IFN-γ, TNF-α, GM-CSF, and IL-22) that induce the activation of macrophages and neutrophils, thereby indirectly aggravating inflammation and tissue damage. This evidence concerns the gene TNF and rheumatoid arthritis.