Natural killer cells and autoimmunity

Natural killer (NK) cells are able to target inflamed tissues, thereby potentially exacerbating autoimmune tissue destruction. However, recent findings suggest that they might also have a protective function during autoimmune disease by editing antigen presenting cells that stimulate autoreactive effector cells and targeting these effectors directly. Genetic evidence, particularly findings in mouse models of autoimmunity, and alterations in the NK cell compartment of patients with autoimmune diseases with and without successful therapy shed some light on the role of this innate lymphocyte subset during autoimmunity. NK cells may play a dual role in autoimmune diseases by initially editing cells of the hematopoietic lineage to curb autoimmunity, but augmenting disease later via inflamed tissue destruction. Therefore, any therapeutic approach, harnessing NK cells during autoimmunity, has to take this functional dichotomy into account. Natural killer (NK) cells constitute a primary defense line against pathogens and can also detect cellular transformation. They can fulfil these functions efficiently following primarily cytokine-mediated activation by dendritic cells (DCs). They recognize infected and transformed cells through germ-line encoded receptors via the loss of MHC class I molecules (missing self) and up-regulation of MHC class I-like molecules (altered self). While these recognition mechanisms allow for rapid responses to control infections and malignant cells prior to initiation of adaptive immune responses, they are potentially dangerous in settings of autoimmune inflammation, which also seems to lead often to an altered-self phenotype, recognizable for NK cells. Even though many studies have addressed the role of NK cells during autoimmune diseases, their role is still not entirely clear.