Regulatory NK cells in autoimmune disease

As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity against tumor cells or infected cells, but also act to regulate the function of other immune cells by secretion of cytokines and chemokines, thus providing surveillance in early defense against viruses, intracellular bacteria and cancer cells. However, the effector function of NK cells must be exquisitely controlled in order to prevent inadvertent attack against self normal cells. The activity of NK cells is defined by integration of signals coming from inhibitory and activation receptors. Inhibitory receptors not only distinguish healthy from diseased cells by recognize self-MHC class I molecules on cell surfaces with “missing-self” model, but also provide an educational signal that generates functional NK cells. NK cells enrich in immunotolerance organ and recent findings of different regulatory NK cell subsets have indicated the unique role of NK cells in maintenance of homeostasis. Once the self-tolerance is broken, autoimmune response may occur. Although data has demonstrated that NK cells play important role in autoimmune disorders, NK cells seemed to act as a two edged weapon and play opposite roles with both regulatory and inducer activity even in the same disease. The precise role and regulatory mechanisms need to be further determined. In this review, we focus on recent research on the association of NK cells and antoimmune diseases, particularly the genetic correlation, the immune tolerance and misrecognition of NK cells, the regulatory function of NK cells, and their potential role in autoimmunity.

► There is genetic correlation of autoimmune diseases with NK cell receptor/ligands. ► NK cells play important role in maintenance of homeostasis. ► Misrecognition of NK cells may contribute to pathogenesis of autoimmune diseases. ► NK cells seemed to act as a two edged weapon in autoimmune diseases.