The Role of Natural Killer Cells in Autoimmunity

Autoimmune diseases are characterized by the selective attack or destruction of a single cell type or tissue by auto-reactive cells of the immune system. The cause of attack of cells is due to loss of self-tolerance of cells like T and B cells which are part of the adaptive immune system. These cells are the major cause of pathology in autoimmunity disorders like type-1 diabetes and rheumatoid arthritis (1,2). Most autoimmune disorders are characterized by sites of chronic inflammation (3,4). In addition to T and B cells, other immune cells like natural killer (NK) cells are also present in the target organs (5-7). NK cells are lymphocytes of the innate immune system, with potent effector functions. NK cells can directly lyse target cells, produce cytokines and interact with other immune cells like DC and T cells (8-10). These functions of NK cells can contribute to autoimmunity either by protecting against or enhancing autoimmunity. NK cells could target and kill auto-reactive T-cells, but NK cells could also recruit auto-reactive T-cells to sites of infection (1,11). The levels of circulating NK cells are lower in patients with autoimmune disorders and have a reduced function (12-15). This reduced function might contribute to autoimmune disorders, by preventing NK cells to functions as that these cells normally would. The reduced function of NK cells, lower numbers and that NK cells are found in the target organs, suggests that NK cells may contribute to autoimmune disorders. The nature of NK cell function in autoimmunity is not clear; NK cells can protect against or enhance autoimmunity. Thus what is the nature of NK cell function in autoimmune diseases and could NK cell function be manipulated to prevent or treat autoimmune diseases? The aim of this review is to discuss the role of NK cells in autoimmune diseases and their use as potential drug targets. The first focus will be on NK cells function under healthy conditions and how self-tolerance is maintained. Next, the role of NK cells in the development and pathology of autoimmune disorders will be discussed using two autoimmunity model systems: type-1 diabetes (T1D) and rheumatoid arthritis (RA). Finally possible therapies for autoimmune diseases using NK cells as targets will be proposed