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Review
. 2019 Oct 17:10:2456.
doi: 10.3389/fimmu.2019.02456. eCollection 2019.

Transcriptional, Epigenetic and Pharmacological Control of JAK/STAT Pathway in NK Cells

Gianluca Scarno  1 , Giuseppe Pietropaolo  1 , Chiara Di Censo  1 , Massimo Gadina  2 , Angela Santoni  1   3 , Giuseppe Sciumè  1
Affiliations
Review

Transcriptional, Epigenetic and Pharmacological Control of JAK/STAT Pathway in NK Cells

Gianluca Scarno et al. Front Immunol. .

Abstract

Differentiation of Natural Killer (NK) cells is a stepwise process having its origin in the bone marrow and proceeding in the periphery, where these cells follow organ specific trajectories. Several soluble factors and cytokines regulate the distinct stages of NK cell differentiation, and ultimately, their functional properties. Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway control distinct aspects of NK cell biology, ranging from development, terminal differentiation, activation, and generation of cells with adaptive properties. Here, we discuss how the recent advances of next generation sequencing (NGS) technology have led to unravel novel molecular aspects of gene regulation, with the aim to provide genomic views of how STATs regulate transcriptional and epigenetic features of NK cells during the different functional stages.

Keywords: JAK; NK cells; STAT; cytokine; innate lymphoid cells; transcription factor; transcriptome.

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Figures

Figure 1
Figure 1
Distinct requirements for STATs in NK cell differentiation. JAK/STAT signals control several aspects of NK cell biology, including development, terminal differentiation, acquisition of effector functions, and generation of adaptive NK cells. NK cell development begins in the bone marrow from committed precursors and it is driven by signals inducing STAT5 activation. In homeostatic conditions STAT5 sustains NK cell survival by direct regulation of Bcl2 expression. STAT5 is also required for terminal differentiation and acquisition of NK cell identity. STAT4 and STAT1 have both specific and shared roles during viral infection. STAT4 controls a network of TFs required for clonal expansion of NK cells during proliferation. STAT4 and STAT1 compete at genomic level for the expression of IFN-γ and other genes. STAT3 has a role in restraining NK cell effector functions by inhibiting perforin, granzyme B, and NKG2D expression.
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