Tissue-resident Eomeshi T-betlo CD56bright NK cells with reduced pro-inflammatory potential are enriched in the human adult 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 CD56^bright NK cells were Eomes^hi T-bet^lo, 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 CD56^dim and blood NK cells. Compared to blood populations, these hepatic CD56^bright 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

from #ENT via xlomafota13 on Inoreader http://ift.tt/2aAEEni
via IFTTT