Tissue‐resident Eomeshi T‐betlo CD56bright NK cells with reduced proinflammatory potential are enriched in the adult human liver. Issue 9 (7th September 2016)

• Record Type: Journal Article
• Authors: Harmon, Cathal; Robinson, Mark W.; Fahey, Ronan; Whelan, Sarah; Houlihan, Diarmaid D.; Geoghegan, Justin; O'Farrelly, Cliona
• Is Part Of: European journal of immunology. Volume 46:Issue 9(2016)
• Page Start: 2111
• Page End: 2120
• Publication Date: 2016-09-07
• Subjects: CD56bright natural killer (NK) cells -- Human liver -- Interferon -- Microenvironment -- Tissue resident; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646559
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : CD56 bright NK cells, which are enriched in adult human liver, are phenotypically and functionally distinct from peripheral blood. Hepatic CD56 bright NK cells have a unique transcriptional profile, Eomes hi Tbet lo, and express the chemokine receptor CXCR6. In addition they produce significantly less IFN‐γ that appears to be repressed by the hepatic microenvironment2 Abstract : 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 have altered expression of the two highly related T‐box transcription factors, T‐bet and eomesodermin (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 (chemokine (C‐X‐C motif) receptor 6), 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.