Transcriptional Control of NK Cell Differentiation and Function

2014 ◽  
pp. 173-187 ◽  
Author(s):  
Victoria Male ◽  
Hugh J. M. Brady
Keyword(s):  
Cell Differentiation ◽  
Transcriptional Control ◽  
Nk Cell ◽  
Nk Cell Differentiation ◽  
And Function

scholarly journals Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3824-3833 ◽  
Author(s):  
Bartosz Grzywacz ◽  
Nandini Kataria ◽  
Magdalena Sikora ◽  
Robert A. Oostendorp ◽  
Elaine A. Dzierzak ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Natural Killer ◽  
Cell Line ◽  
Nk Cell ◽  
Fetal Liver ◽  
Interferon Γ ◽  
Intermediate Phenotype ◽  
Interleukin 7 ◽  
Nk Cell Differentiation ◽  
And Function

AbstractThe stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34+ progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56+ cells based on CD117 and CD94 (CD117highCD94– and CD117low/–CD94+ cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117low/– CD94+ population displayed cytotoxicity and interferon-γ production. Both populations arose from a single CD34+CD38– Lin– cell and their percentages changed over time in a reciprocal fashion, with CD117highCD94– cells predominating early and decreasing due to an increase of the CD117low/–CD94+ population. These 2 subsets represent distinct stages of NKcell differentiation, since purified CD117high CD94– cells give rise to CD117low/–CD94+ cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117highCD94– to CD117low/–CD94+ via an intermediate phenotype (CD117lowCD94low/–). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117low/–CD94+ cells to the intermediate (CD117lowCD94low/–) phenotype. An analogous population of CD56+CD117highCD94– cells was found in cord blood. The identified stages of NK-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human NK cells.

scholarly journals Assessment of Requirements for IL-15 and IFN Regulatory Factors in Uterine NK Cell Differentiation and Function During Pregnancy

2003 ◽  
Vol 171 (6) ◽  
pp. 2937-2944 ◽  
Author(s):  
Ali A. Ashkar ◽  
Gordon P. Black ◽  
Qingxia Wei ◽  
Hong He ◽  
Luchuan Liang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Regulatory Factors ◽  
Nk Cell Differentiation ◽  
And Function

scholarly journals The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation

2021 ◽  
Vol 6 (57) ◽  
pp. eabc9801
Author(s):  
Tim D. Holmes ◽  
Ram Vinay Pandey ◽  
Eric Y. Helm ◽  
Heinrich Schlums ◽  
Hongya Han ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
T Cell ◽  
Nk Cells ◽  
Nk Cell ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Murine Cytomegalovirus ◽  
Nk Cell Differentiation ◽  
And Function

Epigenetic landscapes can provide insight into regulation of gene expression and cellular diversity. Here, we examined the transcriptional and epigenetic profiles of seven human blood natural killer (NK) cell populations, including adaptive NK cells. The BCL11B gene, encoding a transcription factor (TF) essential for T cell development and function, was the most extensively regulated, with expression increasing throughout NK cell differentiation. Several Bcl11b-regulated genes associated with T cell signaling were specifically expressed in adaptive NK cell subsets. Regulatory networks revealed reciprocal regulation at distinct stages of NK cell differentiation, with Bcl11b repressing RUNX2 and ZBTB16 in canonical and adaptive NK cells, respectively. A critical role for Bcl11b in driving NK cell differentiation was corroborated in BCL11B-mutated patients and by ectopic Bcl11b expression. Moreover, Bcl11b was required for adaptive NK cell responses in a murine cytomegalovirus model, supporting expansion of these cells. Together, we define the TF regulatory circuitry of human NK cells and uncover a critical role for Bcl11b in promoting NK cell differentiation and function.

Impaired NK cell differentiation of blood-derived CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis

2003 ◽  
Vol 106 (3) ◽  
pp. 201-212 ◽  
Author(s):  
Diane Briard ◽  
Danièle Brouty-Boyé ◽  
Julien Giron-Michel ◽  
Bruno Azzarone ◽  
Claude Jasmin ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Myeloid Metaplasia ◽  
Nk Cell Differentiation

scholarly journals TH9 cell differentiation, transcriptional control and function in inflammation, autoimmune diseases and cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (43) ◽  
pp. 71001-71012 ◽  
Author(s):  
Yan Li ◽  
Qing Yu ◽  
Zhengguo Zhang ◽  
Jian Wang ◽  
Simin Li ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Autoimmune Diseases ◽  
Transcriptional Control ◽  
And Function ◽  
Th9 Cell

CD27‐deficient mice show normal NK‐cell differentiation but impaired function upon stimulation

2011 ◽  
Vol 89 (7) ◽  
pp. 803-811 ◽  
Author(s):  
Veerle De Colvenaer ◽  
Sylvie Taveirne ◽  
Maarten Delforche ◽  
Magda De Smedt ◽  
Bart Vandekerckhove ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Impaired Function ◽  
Nk Cell Differentiation ◽  
Deficient Mice

scholarly journals Evidence for discrete stages of human natural killer cell differentiation in vivo

2006 ◽  
Vol 203 (4) ◽  
pp. 1033-1043 ◽  
Author(s):  
Aharon G. Freud ◽  
Akihiko Yokohama ◽  
Brian Becknell ◽  
Melissa T. Lee ◽  
Hsiaoyin C. Mao ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Intermediate Stage ◽  
Cell Surface Expression ◽  
Lymphoid Tissues ◽  
Human Natural Killer Cell ◽  
Nk Cell Differentiation

Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues.

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