Abstract
Natural killer (NK) cells are the major lymphocyte subset of the innate immune system. Their ability to mediate anti-tumor cytotoxicity and produce cytokines is well-established. However, the molecular mechanisms associated with the development of human or murine NK cells are not fully understood. Knowledge is being gained about the environmental cues, the receptors that sense the cues, signaling pathways, and the transcriptional programs responsible for the development of NK cells. Specifically, a complex network of transcription factors (TFs) following microenvironmental stimuli coordinate the development and maturation of NK cells. Multiple TFs are involved in the development of NK cells in a stage-specific manner. In this review, we summarize the recent advances in the understandings of TFs involved in the regulation of NK cell development, maturation, and effector function, in the aspects of their mechanisms, potential targets, and functions.
Highlights
Natural killer (NK) cells are cytotoxic lymphocytes that mediate anti-viral and anti-tumor responses [1,2,3]
Both human and murine NK cells primarily arise from self-renewing pluripotent hematopoietic stem cells (HSCs), which reside in bone marrow (BM) and commit to a sequential order of intermediate progenitors [26,27,28]
These results indicate that it regulates the expression of multiple mature markers, Runx3 plays a moderate role in regulating effector functions of NK cells
Summary
Natural killer (NK) cells are cytotoxic lymphocytes that mediate anti-viral and anti-tumor responses [1,2,3]. The significant challenge is to fully define the transcriptional networks that regulate the development, heterogeneity, and effector functions of human NK cells This is essential in order to formulate effective NK cell-based cellular therapies and to augment their effector functions. Cell surface markers were used to define distinct developmental stages of NK cells While these approaches led to significant advancements in our understanding of NK cells, they failed to provide information on the associated molecular mechanisms. Studies using CyTOF demonstrated that there are 6000 to 30,000 distinct NK cell phenotypes within an individual based on 35 different cell surface antigens [21] This approach does not offer any insights into the transcriptional mechanisms that govern the generation of vast heterogeneity among NK cells. We summarize the TFs that control NK cell development and functions
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