scholarly journals mTORC1 and mTORC2 differentially promote natural killer cell development

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Chao Yang ◽  
Shirng-Wern Tsaih ◽  
Angela Lemke ◽  
Michael J Flister ◽  
Monica S Thakar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Development ◽  
Lymphoid Cells ◽  
Innate And Adaptive Immunity ◽  
Mechanistic Target Of Rapamycin

Natural killer (NK) cells are innate lymphoid cells that are essential for innate and adaptive immunity. Mechanistic target of rapamycin (mTOR) is critical for NK cell development; however, the independent roles of mTORC1 or mTORC2 in regulating this process remain unknown. Ncr1iCre-mediated deletion of Rptor or Rictor in mice results in altered homeostatic NK cellularity and impaired development at distinct stages. The transition from the CD27+CD11b− to the CD27+CD11b+ stage is impaired in Rptor cKO mice, while, the terminal maturation from the CD27+CD11b+ to the CD27−CD11b+ stage is compromised in Rictor cKO mice. Mechanistically, Raptor-deficiency renders substantial alteration of the gene expression profile including transcription factors governing early NK cell development. Comparatively, loss of Rictor causes more restricted transcriptome changes. The reduced expression of T-bet correlates with the terminal maturation defects and results from impaired mTORC2-AktS473-FoxO1 signaling. Collectively, our results reveal the divergent roles of mTORC1 and mTORC2 in NK cell development.

scholarly journals A research-driven approach to the identification of novel natural killer cell deficiencies affecting cytotoxic function

Blood ◽  
2020 ◽  
Vol 135 (9) ◽  
pp. 629-637
Author(s):  
Michael T. Lam ◽  
Emily M. Mace ◽  
Jordan S. Orange
Keyword(s):  
Natural Killer Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Development ◽  
Impact Testing ◽  
Primary Immune Deficiency ◽  
Cell Cytotoxicity ◽  
Nk Cell Cytotoxicity

Abstract Natural killer cell deficiencies (NKDs) are an emerging phenotypic subtype of primary immune deficiency. NK cells provide a defense against virally infected cells using a variety of cytotoxic mechanisms, and patients who have defective NK cell development or function can present with atypical, recurrent, or severe herpesviral infections. The current pipeline for investigating NKDs involves the acquisition and clinical assessment of patients with a suspected NKD followed by subsequent in silico, in vitro, and in vivo laboratory research. Evaluation involves initially quantifying NK cells and measuring NK cell cytotoxicity and expression of certain NK cell receptors involved in NK cell development and function. Subsequent studies using genomic methods to identify the potential causative variant are conducted along with variant impact testing to make genotype-phenotype connections. Identification of novel genes contributing to the NKD phenotype can also be facilitated by applying the expanding knowledge of NK cell biology. In this review, we discuss how NKDs that affect NK cell cytotoxicity can be approached in the clinic and laboratory for the discovery of novel gene variants.

Gene Expression Profiling of Natural Killer Cell Subsets Isolated Using Novel MACS Methods.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3911-3911
Author(s):  
Jurgen Schmitz
Keyword(s):  
Gene Expression ◽  
Natural Killer Cell ◽  
Gene Expression Profiling ◽  
Natural Killer ◽  
Microarray Analysis ◽  
Expression Profiling ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Separation Performance

Abstract Natural Killer cells are now regarded as an important (Hokland, Mol Immunol 2005) but heterogenous (Cooper, Blood 2001) lymphocyte subset. Different Natural Killer cell subsets have different functions (Cooper, Blood 2001; Mavilio, PNAS 2005; Trotta, Blood 2005) and further research will be required to identify the role of those NK cell subsets in immune responses. We have developed novel methods, based on magnetic cell sorting, for purification of several NK cell subsets and have evaluated the separation performance of these kits using peripheral blood mononuclear cells from 10 donors. More than 1x105 CD56brightCD16− cells from 1x108 PBMC can be isolated with >70% purity (>85% CD56+CD16−), and more than 1x106 CD56dimCD16+ cells with >94% purity. Additional subsets have been identified based on CD8 expression: >2x106 CD8+ NK cells can be purified with >90% purity. Only limited data has previously been published on gene expression profiling of NK cell subsets using DNA microarrays (Koopman, J Exp Med 2003). We thus have used these MACS sorted NK cell subsets from 3 donors for an immune system specific microarray analysis (“PIQOR Immunology”). Usually gene expression profiling experiments are combined with flow cytometry characterization and functional tests. We used a novel amplification method to perform microarray analysis from mRNA isolated from as little as 1000 cells. Genes for surface molecules known to be differently expressed on NK cell subsets and immune effector molecules produced preferentially by single subsets served as control for the combination of amplification and microarray analysis (CD56, CD16, CD8, CD62L, CD122, Perforin, Granzyme B). Results of the analysis will be shown.

Stage-dependent gene expression profiles during natural killer cell development

Genomics ◽  
2005 ◽  
Vol 86 (5) ◽  
pp. 551-565 ◽  
Author(s):  
Hyung-Sik Kang ◽  
Eun-Mi Kim ◽  
Sanggyu Lee ◽  
Suk-Ran Yoon ◽  
Toshihiko Kawamura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Expression Profiles ◽  
Killer Cell ◽  
Gene Expression Profiles ◽  
Cell Development

scholarly journals TOX2 regulates human natural killer cell development by controlling T-BET expression

Blood ◽  
2014 ◽  
Vol 124 (26) ◽  
pp. 3905-3913 ◽  
Author(s):  
Queenie P. Vong ◽  
Wai-Hang Leung ◽  
Jim Houston ◽  
Ying Li ◽  
Barbara Rooney ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Development ◽  
Human Natural Killer Cell ◽  
Key Points

Key Points Normal maturation of human NK cells requires the expression of TOX2. TOX2 directly regulates the expression of T-BET during human NK cell development.

Natural Killer Cell Inspired AIE Nanoterminator for Blood-Brain-Barrier Crossing via Tight-Junction Modulation and NIR-II Gliomas Theranostics

2020 ◽  
Author(s):  
Guanjun Deng ◽  
Xinghua Peng ◽  
Zhihong Sun ◽  
Wei Zheng ◽  
Jia Yu ◽  
...  
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Intracellular Signaling ◽  
Soft Matter ◽  
Tumor Imaging ◽  
Nk Cell ◽  
Killer Cell ◽  
Light Illumination ◽  
Blood Brain ◽  
Intracellular Signaling Cascade

Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. In this paper, we developed a natural killer cell-mimic AIE nanoterminator (NK@AIEdots) by coating natural kill cell membrane on the AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owning to the AIE and soft-matter characteristics of PBPTV, as-prepared nanoterminator maintained the superior NIR-II brightness (quantum yield ~8%) and good biocompatibility. Besides, they could serve as tight junctions (TJs) modulator to trigger an intracellular signaling cascade, causing TJs disruption and actin cytoskeleton reorganization to form intercellular “green channel” to help themselves crossing Blood-Brain Barriers (BBB) silently. Furthermore, they could initiatively accumulate to glioblastoma cells in the complex brain matrix for high-contrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these nanoterminator under the NIR light illumination. As far as we known, The QY of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots will open new avenue for BBB-crossing delivery.

Sign in / Sign up

Export Citation Format

Share Document