Murine thymic NK cells: A case of identity

Male, Victoria; Brady, Hugh J.M.

doi:10.1002/eji.201747038

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…Finally, we assessed the fidelity of reporter expression by focusing on classical NK (cNK) and tNK cells, which are developmentally different subpopulations with distinctive levels of Gata3 expression (46,47). Following the gating scheme published in the original description of tNK cells (14) (Fig.…”

Section: Bright Vyfp Fluorescence Faithfully Reflects Endogenous Gatamentioning

confidence: 99%

Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

Rao

Kumar

Pulikkottil

et al. 2020

The Journal of Immunology

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Accurately tuned expression levels of the transcription factor GATA-3 are crucial at several stages of T cell and innate lymphoid cell development and differentiation. Moreover, several lines of evidence suggest that Gata3 expression might provide a reliable molecular marker for the identification of elusive progenitor cell subsets at the earliest stages of T lineage commitment. To be able to faithfully monitor Gata3 expression noninvasively at the single-cell level, we have generated a novel strain of knock-in reporter mice, termed GATIR, by inserting an expression cassette encoding a bright fluorescent marker into the 39-untranslated region of the endogenous Gata3 locus. Importantly, in contrast to three previously published strains of Gata3 reporter mice, GATIR mice preserve physiological Gata3 expression on the targeted allele. In this study, we show that GATIR mice faithfully reflect endogenous Gata3 expression without disturbing the development of GATA-3-dependent lymphoid cell populations. We further show that GATIR mice provide an ideal tool for noninvasive monitoring of Th2 polarization and straightforward identification of innate lymphoid cell 2 progenitor populations. Finally, as our reporter is non-gene-destructive, GATIR mice can be bred to homozygosity, not feasible with previously published strains of Gata3 reporter mice harboring disrupted alleles. The availability of hetero-and homozygous Gata3 reporter mice with an exceptionally bright fluorescent marker, allowed us to visualize allelic Gata3 expression in individual cells simply by flow cytometry. The unambiguous results obtained provide compelling evidence against previously postulated monoallelic Gata3 expression in early T lineage and hematopoietic stem cell subsets.

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Section: Bright Vyfp Fluorescence Faithfully Reflects Endogenous Gatamentioning

confidence: 99%

Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

Rao

Kumar

Pulikkottil

et al. 2020

The Journal of Immunology

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Mouse innate resistance to Neospora caninum infection is driven by early production of IFNγ by NK cells in response to parasite ligands

Coombs,

Overacre-Delgoffe,

Bhattacharjee

et al. 2024

mSphere

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Toxoplasma gondii is capable of being transmitted by nearly all warm-blooded animals, and rodents are a major source of parasite dissemination, yet mechanisms driving its broad host range are poorly understood. Although a phylogenetically close relative of T. gondii , Neospora caninum differs from T. gondii in that it does not infect mice and only infects a small number of ruminant and canine species. We recently showed that T. gondii and N. caninum grow similarly in mice during the first 24 h post-infection, but only N. caninum induces an IFNγ-driven response within hours that controls the infection. The goal of the present study was to understand the cellular basis of this rapid response to N. caninum . To do this, we compared immune cell populations at the site of infection 4 h after T. gondii or N. caninum infection in mice. We found that both parasites induced similar frequencies of peritoneal monocytes, while macrophages and dendritic cell populations were not increased compared to uninfected mice. Through a series of knockout mouse experiments, we show that B, T, and NKT cells are not required for immediate IFNγ production and ultimate control of N. caninum infection, suggesting that natural killer (NK) cells are the primary inducers of immediate IFNγ in response to N. caninum. N. caninum infections exhibited significantly more IFNγ + NK cells in the peritoneum compared with T. gondii -infected and uninfected mice. Finally, we demonstrate that differences in early IFNγ production during N. caninum and T. gondii infections in mice are at least partly due to differences in soluble antigen(s) produced by tachyzoites. IMPORTANCE Pathogen differences in host range are poorly understood at the molecular level even though even closely related pathogen species can have dramatically distinct host ranges. Here, we study two related parasite species that have a dramatic difference in their ability to infect mice. Here, we show that soluble proteins from these species determine one driver of this difference: induction of interferon gamma by cells of the innate immune system.

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Murine leupaxin deletion results in spontaneous weight gain, tissue inflammation, and integrin signaling defects

Liu¹

2020

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Murine thymic NK cells: A case of identity

Cited by 3 publications

References 27 publications

Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

Novel, Non–Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

Mouse innate resistance to Neospora caninum infection is driven by early production of IFNγ by NK cells in response to parasite ligands

Murine leupaxin deletion results in spontaneous weight gain, tissue inflammation, and integrin signaling defects

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