Comparative transcriptomics of porcine liver-resident CD8a(dim), liver CD8a(high) and circulating blood CD8a(high) NK cells reveals an intermediate phenotype of liver CD8a(high) NK cells

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 CD8a(high) subset, with a phenotype much like conventional CD8a(high) NK cells found in the peripheral blood, and a specific liver-resident CD8a(dim) 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 CD8a(high) NK cells from peripheral blood (cNK cells), CD8a(high) NK cells isolated from the liver, and the liver-specific CD8a(dim) NK cells. We found that highly expressed transcripts in the CD8a(dim) 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 CD8a(dim) lrNK cells show an immature and anti-inflammatory phenotype. Interestingly, we also observed that the CD8a(high) 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.