Human NK Cell Development: One Road or Many?

Cichocki, Frank; Grzywacz, Bartosz; Miller, Jeffrey S.

doi:10.3389/fimmu.2019.02078

Cited by 107 publications

(93 citation statements)

References 85 publications

(85 reference statements)

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“…The latter is necessary for sensitive detection of pathogen- or tumor-mediated downregulation of selected HLA class I genes. So far, a progenitor/product relationship has been widely assumed for CD56 bright and CD56 dim NK cells respectively, although other possibilities such as a branched model for NK cell development were suggested ( Cichocki et al, 2019 ; Michel et al, 2016 ). Here, employing identical differentiation conditions, ILC1-like NKPs rather than CD56 bright NK cells were able to reconstitute complex NK cell receptor repertoires including NKG2A - KIR + NK cells.…”

Section: Discussionmentioning

confidence: 99%

Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells

Bennstein

Weinhold

Manser

et al. 2020

eLife

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Despite their identification several years ago, molecular identity and developmental relation between human ILC1 and NK cells, comprising group 1 ILCs, is still elusive. To unravel their connection, thorough transcriptional, epigenetic, and functional characterization was performed from umbilical cord blood (CB). Unexpectedly, ILC1-like cells lacked Tbet expression and failed to produce IFNγ. Moreover, in contrast to previously described ILC1 subsets they could be efficiently differentiated into NK cells. These were characterized by highly diversified KIR repertoires including late stage NKG2A-KIR+ effector cells that are commonly not generated from previously known NK cell progenitor sources. This property was dependent on stroma cell-derived Notch ligands. The frequency of the novel ILC1-like NK cell progenitor (NKP) significantly declined in CB from early to late gestational age. The study supports a model in which circulating fetal ILC1-like NKPs travel to secondary lymphoid tissues to initiate the formation of diversified NK cell repertoires after birth.

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Section: Discussionmentioning

confidence: 99%

Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells

Bennstein

Weinhold

Manser

et al. 2020

eLife

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“…NK cells form a unique cellular subset since they are of the lymphoid lineage, more closely related to B and T cells, but act more like an innate immune cell in their function, are therefore often referred to as innate lymphoid cells or ILCs (Figure 2A) (52)(53)(54). NK cells are exceptionally diverse, and I will briefly discuss both their presence in peripheral blood (PB) and tissues ( Figure 2B) (55)(56)(57)(58)(59).…”

Section: Cellular and Tissue Distribution Of Fcγrsmentioning

confidence: 99%

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Murin

2020

Front. Immunol.

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It has been well-established that antibody isotype, glycosylation, and epitope all play roles in the process of antibody dependent cellular cytotoxicity (ADCC). For natural killer (NK) cells, these phenotypes are linked to cellular activation through interaction with the IgG receptor FcγRIIIa, a single pass transmembrane receptor that participates in cytoplasmic signaling complexes. Therefore, it has been hypothesized that there may be underlying spatial and geometric principles that guide proper assembly of an activation complex within the NK cell immune synapse. Further, synergy of antibody phenotypic properties as well as allosteric changes upon antigen binding may also play an as-of-yet unknown role in ADCC. Understanding these facets, however, remains hampered by difficulties associated with studying immune synapse dynamics using classical approaches. In this review, I will discuss relevant NK cell biology related to ADCC, including the structural biology of Fc gamma receptors, and how the dynamics of the NK cell immune synapse are being studied using innovative microscopy techniques. I will provide examples from the literature demonstrating the effects of spatial and geometric constraints on the T cell receptor complex and how this relates to intracellular signaling and the molecular nature of lymphocyte activation complexes, including those of NK cells. Finally, I will examine how the integration of high-throughput and "omics" technologies will influence basic NK cell biology research moving forward. Overall, the goal of this review is to lay a basis for understanding the development of drugs and therapeutic antibodies aimed at augmenting appropriate NK cell ADCC activity in patients being treated for a wide range of illnesses.

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“…A proportion of them express molecules known as tissue-resident markers for T cells, such as CD69 and CD103 (5). The local tissue environment impacts NK cell diversity and function (5,13). The role of tissue localization in human NK cell development and function and how circulating NK cells relate to those in different sites are, however, not yet sufficiently well understood.…”

Section: Introductionmentioning

confidence: 99%

Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection

et al. 2020

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Natural killer (NK) cells play essential roles in immunity to viruses and tumors. Their function is genetically determined but also modulated by environmental factors. The distribution and functional regulation of these cells vary depending on the tissue. NK cell behavior in lymphoid tissues is so far understudied. Non-human primate (NHP) models are essential for the development of therapies and vaccines against human diseases, and access to NHP tissues allows insights into spatial regulations of NK cells. Here, we investigated tissue-specific parameters of NK cells from NHP species, i.e., cynomolgus macaque (Macaca fascicularis), African green monkey (Chlorocebus sabaeus), rhesus macaque (Macaca mulatta), and baboon (Papio anubis). By comprehensive multidimensional analysis of NK cells from secondary lymphoid organs, intestinal mucosa, liver, and blood, we identified tissue-and species-specific patterns of NK cell frequencies, phenotypes, and potential activity. Also, we defined the tissue-specific characteristics of NK cells during infection by the simian immunodeficiency virus. Altogether, our results provide a comprehensive anatomic analysis of NK cells in different tissues of primates at steady-state and during a viral infection.

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Human NK Cell Development: One Road or Many?

Cited by 107 publications

References 85 publications

Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells

Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells

Considerations of Antibody Geometric Constraints on NK Cell Antibody Dependent Cellular Cytotoxicity

Non-human Primate Determinants of Natural Killer Cells in Tissues at Steady-State and During Simian Immunodeficiency Virus Infection

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