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Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells

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Abstract
Natural killer (NK) cells are cells of the innate immunity and play an important role in the defense against viral infections and cancer, but also contribute to shaping adaptive immune responses. Long-lived tissue-resident NK cells have been described in man and mouse, particularly in the liver, contributing to the idea that the functional palette of NK cells may be broader than originally thought, and may include memory-like responses and maintaining tissue homeostasis. Remarkably, liver resident (lr)NK cells in man and mouse show substantial species-specific differences, in particular reverse expression patterns of the T-box transcription factors Eomesodermin (Eomes) and T-bet (Eomes(high)T-bet(low) in man and vice versa in mouse). In pig, compared to blood NK cells which are CD3-CD8 alpha(high) cells, the porcine liver contains an abundant additional CD3-CD8 alpha(dim) NK cell subpopulation. In the current study, we show that this porcine CD3-CD8 alpha(dim) liver NK population is highly similar to its human lrNK counterpart and therefore different from mouse lrNK cells. Like human lrNK cells, this porcine NK cell population shows an Eomes(high)T-bet(low) expression pattern. In addition, like its human counterpart, the porcine liver NK population is CD49e(-) and CXCR6(+). Furthermore, the porcine Eomes(high)T-bet(low) liver NK cell population is able to produce IFN-gamma upon IL-2/12/18 stimulation but lacks the ability to kill K562 or pseudorabies virus-infected target cells, although limited degranulation could be observed upon incubation with K562 cells or upon CD16 crosslinking. All together, these results show that porcine Eomes(high)T-bet(low) NK cells in the liver strongly resemble human lrNK cells, and therefore indicate that the pig may represent a unique model to study the function of these lrNK cells in health and disease.
Keywords
natural killer cells, NK cells, tissue residency, Eomes, T-bet, liver, pig, MEDIATED LYSIS, EXPRESSION, ANTIBODIES, CXCR6, IL-12, PIG

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MLA
De Pelsmaeker, Steffi, et al. “Identification of a Porcine Liver Eomes-High-T-Bet-Low NK Cell Subset That Resembles Human Liver Resident NK Cells.” FRONTIERS IN IMMUNOLOGY, vol. 10, 2019, doi:10.3389/fimmu.2019.02561.
APA
De Pelsmaeker, S., Denaeghel, S., Hermans, L., & Favoreel, H. (2019). Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells. FRONTIERS IN IMMUNOLOGY, 10. https://doi.org/10.3389/fimmu.2019.02561
Chicago author-date
De Pelsmaeker, Steffi, Sofie Denaeghel, Leen Hermans, and Herman Favoreel. 2019. “Identification of a Porcine Liver Eomes-High-T-Bet-Low NK Cell Subset That Resembles Human Liver Resident NK Cells.” FRONTIERS IN IMMUNOLOGY 10. https://doi.org/10.3389/fimmu.2019.02561.
Chicago author-date (all authors)
De Pelsmaeker, Steffi, Sofie Denaeghel, Leen Hermans, and Herman Favoreel. 2019. “Identification of a Porcine Liver Eomes-High-T-Bet-Low NK Cell Subset That Resembles Human Liver Resident NK Cells.” FRONTIERS IN IMMUNOLOGY 10. doi:10.3389/fimmu.2019.02561.
Vancouver
1.
De Pelsmaeker S, Denaeghel S, Hermans L, Favoreel H. Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells. FRONTIERS IN IMMUNOLOGY. 2019;10.
IEEE
[1]
S. De Pelsmaeker, S. Denaeghel, L. Hermans, and H. Favoreel, “Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells,” FRONTIERS IN IMMUNOLOGY, vol. 10, 2019.
@article{8636357,
  abstract     = {{Natural killer (NK) cells are cells of the innate immunity and play an important role in the defense against viral infections and cancer, but also contribute to shaping adaptive immune responses. Long-lived tissue-resident NK cells have been described in man and mouse, particularly in the liver, contributing to the idea that the functional palette of NK cells may be broader than originally thought, and may include memory-like responses and maintaining tissue homeostasis. Remarkably, liver resident (lr)NK cells in man and mouse show substantial species-specific differences, in particular reverse expression patterns of the T-box transcription factors Eomesodermin (Eomes) and T-bet (Eomes(high)T-bet(low) in man and vice versa in mouse). In pig, compared to blood NK cells which are CD3-CD8 alpha(high) cells, the porcine liver contains an abundant additional CD3-CD8 alpha(dim) NK cell subpopulation. In the current study, we show that this porcine CD3-CD8 alpha(dim) liver NK population is highly similar to its human lrNK counterpart and therefore different from mouse lrNK cells. Like human lrNK cells, this porcine NK cell population shows an Eomes(high)T-bet(low) expression pattern. In addition, like its human counterpart, the porcine liver NK population is CD49e(-) and CXCR6(+). Furthermore, the porcine Eomes(high)T-bet(low) liver NK cell population is able to produce IFN-gamma upon IL-2/12/18 stimulation but lacks the ability to kill K562 or pseudorabies virus-infected target cells, although limited degranulation could be observed upon incubation with K562 cells or upon CD16 crosslinking. All together, these results show that porcine Eomes(high)T-bet(low) NK cells in the liver strongly resemble human lrNK cells, and therefore indicate that the pig may represent a unique model to study the function of these lrNK cells in health and disease.}},
  articleno    = {{2561}},
  author       = {{De Pelsmaeker, Steffi and Denaeghel, Sofie and Hermans, Leen and Favoreel, Herman}},
  issn         = {{1664-3224}},
  journal      = {{FRONTIERS IN IMMUNOLOGY}},
  keywords     = {{natural killer cells,NK cells,tissue residency,Eomes,T-bet,liver,pig,MEDIATED LYSIS,EXPRESSION,ANTIBODIES,CXCR6,IL-12,PIG}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{Identification of a porcine liver eomes-high-T-bet-low NK cell subset that resembles human liver resident NK cells}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2019.02561}},
  volume       = {{10}},
  year         = {{2019}},
}

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