Identification of a Porcine Liver EomeshighT-betlow NK Cell Subset That Resembles Human Liver Resident NK Cells

Pelsmaeker, Steffi De; Denaeghel, Sofie; Hermans, Leen; Favoreel, Herman

doi:10.3389/fimmu.2019.02561

Cited by 10 publications

(15 citation statements)

References 42 publications

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“…Together with our current data, this reinforces the hypothesis that IL-10 may contribute to antiviral innate immunity mediated by NK cells (51). Our current data that IL-10 increases NK cell cytotoxicity in pig are thus in line with similar observations in human (43)(44)(45), and further support the idea that experimental work on porcine NK cells may generate insights that are also relevant toward a better understanding of human NK cell biology (24,52,53).…”

Section: Discussionsupporting

confidence: 90%

β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity

et al. 2021

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Beta-glucans are naturally occurring polysaccharides present in cell walls of fungi, yeast, bacteria, cereals, seaweed, and algae. These microbe-associated molecular patterns (MAMPs) possess immunomodulatory properties. In human, it has been suggested that NK cells can be activated by β-glucans. Here, we aimed to elucidate whether β-glucans modulate porcine NK cell responses in vitro and if so, how these effects are mediated. We investigated the effect of two β-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of β-glucans to purified porcine NK cells did not affect cytotoxicity of these cells against K562 target cells. However, when using PBMC instead of purified NK cells, β-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon β-glucan priming. Further analysis showed that monocytes secrete TNF-α, IL-6, and IL-10 upon β-glucan addition. Of these, IL-10 turned out to play a critical role in β-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the β-glucan-induced increase in cytotoxicity. Furthermore, addition of recombinant IL-10 to purified NK cells was sufficient to enhance cytotoxicity. In conclusion, we show that β-glucans trigger IL-10 secretion by porcine monocytes, which in turn leads to increased NK cell cytotoxicity, and thereby identify IL-10 as a potent stimulus of porcine NK cell cytotoxicity.

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Section: Discussionsupporting

confidence: 90%

β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity

et al. 2021

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“…NK cell degranulation based on CD107a mobilisation is an indicator of cytolytic activity ( 33 ). In this study, peripheral blood mononuclear cells (PBMC) were stimulated with recombinant porcine (rp)IL-2, rpIL-12 and rpIL-18 to differentiate NK cells into cytotoxic effectors ( 34 ). Porcine NK cells were defined as CD3 - CD8α + ( Figure 6A ).…”

Section: Resultsmentioning

confidence: 99%

Fc-Mediated Functions of Porcine IgG Subclasses

et al. 2022

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The pig is an important agricultural species and powerful biomedical model. We have established the pig, a large natural host animal for influenza with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies. Antibodies provide protection through neutralization and recruitment of innate effector functions through the Fc domain. However very little is known about the Fc-mediated functions of porcine IgG subclasses. We have generated 8 subclasses of two porcine monoclonal anti influenza hemagglutinin antibodies. We characterized their ability to activate complement, trigger cytotoxicity and phagocytosis by immune cells and assayed their binding to monocytes, macrophages, and natural killer cells. We show that IgG1, IgG2a, IgG2b, IgG2c and IgG4 bind well to targeted cell types and mediate complement mediated cellular cytotoxicity (CDCC), antibody dependent cellular cytotoxicity (ADCC) and antibody mediated cell phagocytosis (ADCP). IgG5b and IgG5c exhibited weak binding and variable and poor functional activity. Immune complexes of porcine IgG3 did not show any Fc-mediated functions except for binding to monocytes and macrophages and weak binding to NK cells. Interestingly, functionally similar porcine IgG subclasses clustered together in the genome. These novel findings will enhance the utility of the pig model for investigation of therapeutic antibodies.

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“…The abundant differences between human and mice lrNK cells (20) complicate extrapolation of data generated on murine lrNK cells to man. Interestingly, we recently identified two subpopulations of NK cells in the porcine liver (21). We described a CD8a high subpopulation, with a phenotype much like conventional CD8a high NK cells found in the peripheral blood, and an abundant liver-resident CD8a dim subpopulation, which strongly resembles human lrNK cells (21).…”

Section: Introductionmentioning

confidence: 79%

“…Interestingly, we recently identified two subpopulations of NK cells in the porcine liver (21). We described a CD8a high subpopulation, with a phenotype much like conventional CD8a high NK cells found in the peripheral blood, and an abundant liver-resident CD8a dim subpopulation, which strongly resembles human lrNK cells (21). Indeed, like their human counterparts, porcine CD8a dim lrNK cells are Eomes high T-bet low CXCR6 + CD49eand there are indications for partial plasticity between porcine cNK cells and lrNK cells (21).…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells

Hermans,

Denaeghel,

Jansens

et al. 2023

Front. Immunol.

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Liver-resident NK (lrNK) cells have been studied in humans as well as in mice. Unfortunately, important differences have been observed between murine and human lrNK cells, complicating the extrapolation of data obtained in mice to man. We previously described two NK cell subsets in the porcine liver: A CD8αhigh subset, with a phenotype much like conventional CD8αhigh NK cells found in the peripheral blood, and a specific liver-resident CD8αdim subset which phenotypically strongly resembles human lrNK cells. These data suggest that the pig might be an attractive model for studying lrNK cell biology. In the current study, we used RNA-seq to compare the transcriptome of three porcine NK cell populations: Conventional CD8αhigh NK cells from peripheral blood (cNK cells), CD8αhigh NK cells isolated from the liver, and the liver-specific CD8αdim NK cells. We found that highly expressed transcripts in the CD8αdim lrNK cell population mainly include genes associated with the (adaptive) immune response, whereas transcripts associated with cell migration and extravasation are much less expressed in this subset compared to cNK cells. Overall, our data indicate that CD8αdim lrNK cells show an immature and anti-inflammatory phenotype. Interestingly, we also observed that the CD8αhigh NK cell population that is present in the liver appears to represent a population with an intermediate phenotype. Indeed, while the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, in particular CXCR6. The current, in-depth characterization of the transcriptome of porcine liver NK cell populations provides a basis to use the pig model for research into liver-resident NK cells.

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Identification of a Porcine Liver EomeshighT-betlow NK Cell Subset That Resembles Human Liver Resident NK Cells

Cited by 10 publications

References 42 publications

β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity

β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity

Fc-Mediated Functions of Porcine IgG Subclasses

Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells

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