Molecular Regulation of NK Cell Maturation

Abstract

Natural killer (NK) cells are innate lymphocytes specialized in immune surveillance against tumors and infections. To reach their optimal functional status, NK cells must undergo a process of maturation from immature to mature NK cells. Genetically modified mice, as well as in vivo and in vitro NK cell differentiation assays, have begun to reveal the landscape of the regulatory network involved in NK cell maturation, in which a balance of cytokine signaling pathways leads to an optimal coordination of transcription factor activity. An increased understanding of NK cell maturation will greatly promote the development and application of NK cell-based clinical therapy. Thus, in this review, we summarize the dynamics of NK cell maturation, describe recently identified factors involved in the regulation of the NK cell maturation process, including cytokines and transcription factors, and discuss the importance of NK cell maturation in health and disease.

A Longitudinal Epigenetic Aging and Leukocyte Analysis of Simulated Space Travel: The Mars-500 Mission

“…This finding is in line with previous studies that demonstrate increased cell death and decreased cytotoxicity in NK cells following long-duration space-travel exposures ( Bigley et al, 2019 ; Li et al, 2013 ). Given the role that NK cells play in the prevention of latent virus reactivation and tumor surveillance, these findings could be concerning for the long-term well-being of astronauts ( Bi and Wang, 2020 ). Although the decreased hematologic cancer risk suggested by our epiTOC2 results seems to be at odds with our NK cell findings, it is important to highlight that the epiTOC2 changes were no longer significant post-mission, but the NK findings were.…”

Immunology of Aging: the Birth of Inflammaging

“…It should be noted that more diversity exists in the innate immune system than initially believed. The cells composing this immune arm are the neutrophils, monocytes, macrophages, NK cells, and some other cells not always well specified [ 89 – 93 ]. Their functions are also well diversified to answer to a multitude of challenges even if the response happens in a non-specific way and with a relatively limited number of effectors [ 94 ].…”

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“…Natural killer (NK) cells are critical effectors of the host innate immune system, and they can directly lyse pathogen-infected and injured cells (88). NK cells have been determined to participate in caner immunology (89,90). Using a B-cell knockout mice model, Inoue and colleagues demonstrated that EL-4 gag tumor cells stimulated B cells to secrete IL-10, which in turn inhibited IFN-g production and tumor elimination by NK cells (60).…”