NK cells - Dr. Jekyll and Mr. Hyde in autoimmune rheumatic diseases

Natural killer (NK) cells belong to innate immune system that are large granular lymphocytes differentiating from the common lymphoid progenitors. These cells were first identified by their functional response against tumor cells and virus-infected cells. That notwithstanding, NK cells are able to affect both adaptive and innate immune arms and modulate a wide range of immune cells. As a consequence, NK cells are capable of bridging between the innate and adaptive immune responses. The effector cytokines as well as direct cell-cell cytotoxicity by NK cells have been shown to be involved in the regulation of the immune responses and might participate in the etiopathogenesis of several disorders, particularly autoimmune rheumatic diseases (AIRDs), such as Ankylosing spondylitis (AS), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Behcet's disease (BD), Systemic sclerosis (SSc), and psoriasis. Nonetheless, NK cells demonstrate both harmful and protective functions during autoimmune diseases pathogenesis based on the subset of NK cell as well as disease microenvironment and disease phase or genetic/environmental stimuli. Here in this review, we intend to go through the recent findings in the etiology and pathogenesis of AIRDs and discuss about their clinical potential to be utilized as targets for the sake of therapy in the context of such disorders.