The localization and migration of natural killer cells in health and disease

Natural killer (NK) cells comprise a finite lymphocyte lineage with distinctive gene expression patterns. Natural killer (NK) cells develop in the bone marrow (BM) and are not static but populate secondary and primary lymphoid organs. A unique feature of NK cells is their expression of activating and inhibitory receptors, which allow them to respond either when ligands for activating receptors are upregulated or when ligands for inhibitory receptors are downregulated. The unique transcriptome of NK cells renders them capable of protecting the host from a vast array of disease states. Their undisputed importance in host protection is conferred by their ability to eliminate unhealthy cells. However, in order for NK cells to exert their effects, they need to be strategically located at the right places. This chapter provides an overview of the current understanding of the localization of NK cell populations and their ability to migrate in response to homeostatic and pathological conditions. NK cells develop in the BM, which they exit using specific molecular interactions. Exit from the BM is followed by localization to a number of tissues, including secondary lymphoid organs. Within each tissue, NK cells often acquire unique function and phenotype that is regulated by the local microenvironment. Their localization is primarily directed by the action of chemokines and therefore is in tight association with the activation status of the organism. Changes in chemokine expression during disease results in further NK cell mobilization and allows them to protect the host from infection and malignancy. Thus, from their time of production until their end, NK cells travel exhaustively over long distances and visit places that influence their already dynamic life.