Regulation of Murine Natural Killer Cell Development

Abstract

Natural killer (NK) cells are effector lymphocytes of the innate immune system that are known for their ability to kill transformed and virus-infected cells. NK cells originate from hematopoietic stem cells in the bone marrow, and studies on mouse models have revealed that NK cell development is a complex, yet tightly regulated process, which is dependent on both intrinsic and extrinsic factors. The development of NK cells can be broadly categorized into two phases: lineage commitment and maturation. Efforts to better define the developmental framework of NK cells have led to the identification of several murine NK progenitor populations and mature NK cell subsets, each defined by a varied set of cell surface markers. Nevertheless, the relationship between some of these NK cell subsets remains to be determined. The classical approach to studying both NK cell development and function is to identify the transcription factors involved and elucidate the mechanistic action of each transcription factor. In this regard, recent studies have provided further insight into the mechanisms by which transcription factors, such as ID2, FOXO1, Kruppel-like factor 2, and GATA-binding protein 3 regulate various aspects of NK cell biology. It is also becoming evident that the biology of NK cells is not only transcriptionally regulated but also determined by epigenetic alterations and posttranscriptional regulation of gene expression by microRNAs. This review summarizes recent progress made in NK development, focusing primarily on transcriptional regulators and their mechanistic actions.

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

“…In mice, commonly used surface markers to identify NK cells are NKp46, CD49b (DX5), and CD161 (NK1.1) gated on CD3-negative cells. In some mouse strains, such as BALB/c, NK cells are identified only by CD49b and NKp46, as these strains have allelic variants of the NK1.1 and do not react with the anti-NK1.1 antibody PK136 (36)(37)(38)(39). In contrast to human NK cells, the surface density of CD27 and CD11b can be used to subdivide murine NK cells into four subsets that define different levels of maturation: CD11b low CD27 low , CD11b low CD27 high , CD11b high CD27 high , and CD11b high CD27 low (40,41).…”

Tbet promotes NK cell egress from the bone marrow and CXCR6 expression in immature NK cells

“…1a). Within the lineagenegative NK1.1 + compartment, we defined CD11bcells as immature (iNK) cells, further subdividing the CD11b + mature (mNK) compartment by their expression of CD27 into a CD27 + subset of intermediate maturity, which for simplicity is sometimes called "mNK1", and a more mature CD27subset called "mNK2" (Kim et al, 2002;Chiossone et al, 2009;Goh and Huntington, 2017). Eomes -CD49a + cells, suggested to represent ILC1, have previously been reported within the Lineage-negative NK1.1+ bone marrow compartment (Klose et al, 2014), although other studies have failed to find a prominent ILC1 population within this gate (Turchinovich et al, 2018;Wang et al, 2018).…”

V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity

“…NK cells are considered innate immune cells since they express germline-encoded antigen receptors and their development does not need RAG expression or V(D)J recombination [55-58]. Paradoxically, NK cells often have V(D)J rearrangements at AgR loci and RAG reporters showed that ∼40% of NK cells develop from RAG-expressing common lymphoid precursors [59-63].…”