Natural Killer Cells--An Epigenetic Perspective of Development and Regulation.

Alexander Schenk,Philipp Zimmer,Wilhelm Bloch

doi:10.3390/ijms17030326

Alexander Schenk, Philipp Zimmer + Show 1 more

Open Access

https://doi.org/10.3390/ijms17030326

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Abstract

Based on their ability to recognize and eliminate various endo- and exogenous pathogens as well as pathological alterations, Natural Killer (NK) cells represent an important part of the cellular innate immune system. Although the knowledge about their function is growing, little is known about their development and regulation on the molecular level. Research of the past decade suggests that modifications of the chromatin, which do not affect the base sequence of the DNA, also known as epigenetic alterations, are strongly involved in these processes. Here, the impact of epigenetic modifications on the development as well as the expression of important activating and inhibiting NK-cell receptors and their effector function is reviewed. Furthermore, external stimuli such as physical activity and their influence on the epigenetic level are discussed.

Highlights

Natural Killer CellsNatural killer cells (NK cells) are historically named by their ability to kill target cells without prior priming on a “natural” way [1]
Based on their ability to recognize and eliminate various endo- and exogenous pathogens as well as pathological alterations, Natural Killer (NK) cells represent an important part of the cellular innate immune system
Cichocki et al [22] found the miRNA miR-181 to be an important regulatory element in the development of NK cells. This was shown by a knockdown of miR-181, which was associated with a decreased differentiation of hemopoietic progenitor cells (HPCs) to mature NK cells, whereas an over-expression of miR-181 led to an increased differentiation into NK cells [22]

Summary

Natural Killer Cells

Natural killer cells (NK cells) are historically named by their ability to kill target cells without prior priming on a “natural” way [1]. IFN-γ secretion enhances the NK cell activity and regulates the innate and adaptive immune system by stimulating macrophages or enhancing the cytotoxicity of CD8+ T-lymphocytes [5,6]. The effector function of NK cells is regulated by an orchestra of activating and inhibitory receptors on the cell surface. These receptors are encoded by the germ line and recognize structures of high molecular weight [9]. The second effector molecule, granzyme B, is a serine protease with similarities to the apoptotic cysteine protease family (caspase) [11] It induces DNA damage by direct and indirect procaspase activation and initiates cell death of the target cells [12]

Epigenetic Modifications

Epigenetic Modifications in NK Cell Development

Epigenetic Regulation of NK Effector Function

Epigenetic Regulation of NK Cell Receptors

Findings

Conclusions