Natural killer cells in inflammation and autoimmunity

First described 40 years ago, natural killer (NK) cells represent the founding members of the innate lymphoid cell (ILC) family. They were initially defined by their ability to kill cancer cells of hematopoietic origin. More recently, NK cells are recognized not only for their ability to kill infected or malignant cells, but also for mediating cytotoxicity against a range of normal immune cells. They thereby play an important physiological role in controlling immune responses and maintaining homeostasis. Besides cytotoxic activity, NK cells activation is accompanied by secretion of pro-inflammatory cytokines. Hence, NK cells have the potential to act both in driving inflammation and in restricting adaptive immune responses that may otherwise lead to excessive inflammation or even autoimmunity. Here, we highlight how NK cell activity is linked to inflammasome activation and review new molecular insights to the roles of NK cells in inflammation and autoimmunity. Furthermore, in light of new insights to NK cell differentiation and memory, we deliberate on how distinct NK cell subsets may impact immunoregulatory functions. Hypothetically, memory-like or adaptive NK cells could drive NK cell-mediated autoreactive diseases. Together, new findings underscore the complex yet important physiological roles of NK cells in both promoting inflammation and exerting immunoregulation and maintenance of immune homeostasis. Insights raise intriguing questions as to how NK cells themselves maintain self-tolerance.