Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human

Chen, Yi‐Ping Phoebe; Ye, Weijian; Tan, Wei Jian; Yong, Kylie Su Mei; Liu, Min; Tan, Shaohua; Loh, Eva; Chang, Kenneth; Tan, Thiam Chye; Preiser, Peter R.; Chen, Jianzhu

doi:10.1038/srep15118

Cited by 25 publications

(26 citation statements)

References 20 publications

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“…1b), consistent with reports that resident microglia express lower levels of Lysm compared to mature circulating myeloid cells2830. NK cells can be differentiated from both lymphoid and myeloid progenitors31 and whilst not a major population infiltrating the eye during EIU25, we included them in the analysis due to their expression of CD11b.…”

Section: Resultssupporting

confidence: 70%

Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye

Gardner¹,

Liyanage²,

Cristante³

et al. 2017

Sci Rep

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Hypoxia inducible factors (HIFs) are ubiquitously expressed transcription factors important for cell homeostasis during dynamic oxygen levels. Myeloid specific HIFs are crucial for aspects of myeloid cell function, including their ability to migrate into inflamed tissues during autoimmune disease. This contrasts with the concept that accumulation of myeloid cells at ischemic and hypoxic sites results from a lack of chemotactic responsiveness. Here we seek to address the role of HIFs in myeloid trafficking during inflammation in a mouse model of human uveitis. We show using mice with myeloid-specific Cre-deletion of HIFs that myeloid HIFs are dispensable for leukocyte migration into the inflamed eye. Myeloid-specific deletion of Hif1a, Epas1, or both together, had no impact on the number of myeloid cells migrating into the eye. Additionally, stabilization of HIF pathways via deletion of Vhl in myeloid cells had no impact on myeloid trafficking into the inflamed eye. Finally, we chemically induce hypoxemia via hemolytic anemia resulting in HIF stabilization within circulating leukocytes to demonstrate the dispensable role of HIFs in myeloid cell migration into the inflamed eye. These data suggest, contrary to previous reports, that HIF pathways in myeloid cells during inflammation and hypoxia are dispensable for myeloid cell tissue trafficking.

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Section: Resultssupporting

confidence: 70%

Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye

Gardner¹,

Liyanage²,

Cristante³

et al. 2017

Sci Rep

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“…It was and is still commonly believed that NK cells derive from CLPs, as demonstrated in numerous studies and confirmed by leaders in the field of innate lymphoid cells (11)(12)(13). However, recent studies showed that differentiation from the human common myeloid progenitor into mature NK cells is also possible, not only in vitro in the presence of appropriate cytokines and stromal cells (14), but also in a humanized mouse model (15). This adds to the growing insight into a greater plasticity of hematopoiesis than previously thought.…”

Section: Origin Of Cd56 Bright Nk Cellsmentioning

confidence: 92%

Human CD56bright NK Cells: An Update

Michel

Poli

Cuapio

et al. 2016

The Journal of Immunology

303

261

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Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56brightCD16−/dim NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56bright NK cells in health and disease and briefly discuss the current controversies surrounding them.

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“…injection of human peripheral blood mononuclear cells (PBMCs) into mice (Hu-PBL- scid ) (Duchosal et al 1992; Harui et al 2011; King et al 2008; Tary-Lehmann et al 1995), injecting CD34 + HSCs obtained from human fetal liver (FL), umbilical cord blood (UBC), bone marrow (BM) or granulocyte-colony-stimulating factor (G-CSF) mobilised peripheral blood (Hu-SRC- scid ) (Brehm et al 2010; Chen et al 2009, 2012, 2015; Keng et al 2015; Yong et al 2016), or i.v. injection of FL HSCs and BM cells paired with transplantation of matching FL and thymus under the kidney capsule to obtain a BM/liver/thymus (BLT) mouse model (Brainard et al 2009; Covassin et al 2013; Denton et al 2008; Lan et al 2004, 2006; Melkus et al 2006; Tonomura et al 2008).…”

Section: Evolving History Of Humanized Micementioning

confidence: 99%

Humanized Mice as Unique Tools for Human-Specific Studies

Yong

Her

Chen

2018

Arch. Immunol. Ther. Exp.

Self Cite

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With an increasing human population, medical research is pushed to progress into an era of precision therapy. Humanized mice are at the very heart of this new forefront where it is acutely required to decipher human-specific disease pathogenesis and test an array of novel therapeutics. In this review, “humanized” mice are defined as immunodeficient mouse engrafted with functional human biological systems. Over the past decade, researchers have been conscientiously making improvements on the development of humanized mice as a model to closely recapitulate disease pathogenesis and drug mechanisms in humans. Currently, literature is rife with descriptions of novel and innovative humanized mouse models that hold a significant promise to become a panacea for drug innovations to treat and control conditions such as infectious disease and cancer. This review will focus on the background of humanized mice, diseases, and human-specific therapeutics tested on this platform as well as solutions to improve humanized mice for future clinical use.

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Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in Human

Cited by 25 publications

References 20 publications

Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye

Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye

Human CD56bright NK Cells: An Update

Humanized Mice as Unique Tools for Human-Specific Studies

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