Unconventional functions of natural killer cells in homeostasis and disease

NK cells are classically defined by their rapid cytotoxicity against tumor cells and infected cells and by early inflammatory cytokine production. However, unconventional roles for NK cells as regulators of immunity and tissue homeostasis have recently been uncovered. Beyond their classical roles, NK cells can orchestrate leukocyte trafficking, curtail responses of other immune cells, remove protein aggregates, support pregnancy, and contribute to healthy tissue regeneration. We discuss the importance of these myriad functional activities of NK cells in infection, cancer, autoimmunity, atopic and allergic disease, pregnancy, tissue injury, and neurodegenerative diseases. The functional pleiotropy of NK cells provides new avenues of translational utility for these innate lymphocytes and represents an unexplored complexity in conventional clinical applications of NK cells against infection and cancer.