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.

Highlights

  • Natural Killer (NK) cells are the founding members of the innate lymphoid cell (ILC) family and represent the innate counterpart of cytotoxic T lymphocytes [1, 2]

  • The role of the Janus kinases (JAKs)/signal transducer and activator of transcription (STAT) dependent signals on NK cells and other ILCs has been discussed in recent reviews [16, 17, 21]; we focus on the molecular mechanisms underlying NK cell differentiation in physiological and pathological contexts

  • Manipulation of cytokine signaling in NK cells and other ILCs is drawing a growing interest for the treatment of inflammatory diseases and cancer [74, 75]

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Summary

Introduction

Natural Killer (NK) cells are the founding members of the ILC family and represent the innate counterpart of cytotoxic T lymphocytes [1, 2]. Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway control NK cell development, terminal differentiation, acquisition of effector phenotype up to generation of cells with adaptive features able to provide secondary responses [16, 17]. Conditional deletion of Stat5 in Ncr1-expressing cells allows to eliminate the confounding effects related to lymphopenia and inflammation observed in mice carrying germline ablation; in these settings, both development and survival of NK cells remain highly impaired [36].

Results
Conclusion

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