http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999796/ Conclusion While inappropriate activation of cells of the adaptative immune response was mainly reported in autoimmune diseases, numerous observations suggest a role for NK cells in these disorders. To date, NK cells have not been specifically targeted by treatments of autoimmune diseases. However, some biotherapies are associated with changes in the circulating NK compartment. For example, daclizumab (anti-IL-2Rα) in multiple sclerosis is associated with an increase in the number of CD56bright NK cells.56 The same change is observed in the treatment of uveitis with daclizumab.57 Interestingly, the expansion of blood NK cells has been found to be correlated with the suppression of disease activity, and NK cells isolated from patients during treatment were able to kill autologous-activated T cells.56 From another point of view, NK cells play an important role, through ADCC, in the efficacy of monoclonal antibodies used to treat human diseases.38 Thus, identifying the modifications of NK cells and the role of NK cells in autoimmune diseases will help to define new therapeutic targets and to optimize the efficiency of current biotherapies in such indications. It has been suggested that NK cells have a disease-promoting or a disease-controlling role in autoimmune diseases, depending on the disease and the NK cell subset analysed. A disease-controlling role is clearly suggested by studies in SLE patients in which circulating NK cells are reduced in number and functions. These abnormalities have been shown to correlate with some clinical manifestations of the disease. Such modifications of NK cells mirror the protective role of NK cells proposed in the model of multiple sclerosis where an increase in the numbers of circulating NK cells correlates with remission of the disease. However, despite clinical correlative evidence, the mechanisms by which NK cells control autoimmune disease remain unknown. Moreover, it is difficult to reconcile the dual NK cell roles in different autoimmune diseases. Perhaps NK cells can have either a protective or a disease-promoting role in a given autoimmune disease at different stages of the disease (e.g. onset and/or progression) in a several-year-long process. Thus, forthcoming studies should focus on tissue NK cells and NK cell interactions with other immune cells at sites of inflammation at different phases of the development of autoimmune diseases.