Abstract
NK cell maturation is a continuous process, which initiates in the bone marrow and proceeds in peripheral tissues, where NK cells follow distinct differentiation routes. Drastic phenotypic changes are observed during progression from precursors to mature NK cells, including changes of expression and functionalities of several chemoattractant receptors. Upon differentiation, mature NK cells migrate outside the bone marrow; as well, peculiar subsets of NK cells can also home back to or localize in this anatomic compartment to play specific functions. In humans, NK cells with a tissue resident phenotype have been identified in bone marrow, sharing similarities with tissue resident memory CD8+ T cells; while in mouse, long-lived NK cells undergo homeostatic proliferation in this site during viral infections. The mechanisms underlying NK cell subset localization in the bone marrow have only recently started to be investigated, especially in pathological settings such as tumors or infections. In this review, we discuss the phenotype and function of NK cells as well as their requirements for bone marrow maintenance and/or homing.
Highlights
Natural Killer (NK) cells are innate lymphocytes able to recognize and kill cancer or virus-infected cells [1]
Studies in mice indicated that systemic type I IFN induction by poly(I:C) treatment, LCMV and MCMV infections elicit NK cell responses [47]. These results suggested that one systemic IFN-α/β induction is required to activate blast NK cell precursors located in bone marrow (BM) and drive their efflux to peripheral compartments leading to increased NK cell cytotoxic activity and appearance of blast NK cells in the spleen
It would be of great importance to understand if a similar expansion of memory-like populations could be observed during cancer growth, since experienced BM NK cells of cancer patients may be potentially able to mediating continuous surveillance against the recurrence of cancer
Summary
Natural Killer (NK) cells are innate lymphocytes able to recognize and kill cancer or virus-infected cells [1]. They account for 5–20% of the mononuclear cells of the peripheral blood and the spleen. They produce cytokines, among which interferon (IFN)-γ delivers signals to the innate component of the immune system, which activate the inflammatory process in defense of the organism. Conventional NK cells appear to be the only cytotoxic cells, while all the other ILCs follow the pattern of helper CD4 T cells and produce cytokines and other soluble factors that help adaptive immune response development
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