Tissue-resident Eomeshi T-betlo CD56bright NK cells with reduced proinflammatory potential are enriched in the adult human liver

The adult human liver is enriched with natural killer (NK) cells, accounting for 30–50% of hepatic lymphocytes which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells with altered expression of the two highly related T-box transcription factors, T-bet and Eomes. Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations. Hepatic NK cells were isolated from donor liver perfusates and biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56bright NK cells were Eomeshi T-betlo, a phenotype virtually absent from peripheral blood. These NK cells express the chemokine receptor CXCR6, a marker of tissue residency, which is absent from hepatic CD56dim and blood NK cells. Compared to blood populations, these hepatic CD56bright NK cells have increased expression of activatory receptors (NKp44, NKp46 and NKG2D). They show reduced ability to produce IFN-γ but enhanced degranulation in response to challenge with target cells. This functionally distinct population of hepatic NK cells constitutes 20–30% of the total hepatic lymphocyte repertoire and represents a tissue-resident immune cell population adapted to the tolerogenic liver microenvironment. This article is protected by copyright. All rights reserved