title: The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function.
abstract: The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α+and NKP46+NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role.
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Conroy
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: Vivienne
authors.initials: V
authors.lastname: Fitzgerald
authors.affiliation: School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Doyle
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: Shauna
authors.initials: S
authors.lastname: Channon
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: Zivile
authors.initials: Z
authors.lastname: Useckaite
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Gilmartin
authors.affiliation: Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.affiliation: Gastro-intestinal Medicine and Surgery, St. James's Hospital, Dublin, Ireland; and.
authors.forename: Narayanasamy
authors.initials: N
authors.lastname: Ravi
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland.|Gastro-intestinal Medicine and Surgery, St. James's Hospital, Dublin, Ireland; and.
authors.forename: John V
authors.initials: JV
authors.lastname: Reynolds
authors.affiliation: Department of Surgery, Trinity Translational Medicine Institute, St. James's Hospital, Trinity College Dublin, Ireland; jlysaght@tcd.ie.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lysaght
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000209:etiology / Q000276:immunology*; D000368:Aged; D002470:Cell Survival; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004938:Esophageal Neoplasms / Q000097:blood / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D050152:Intra-Abdominal Fat / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000032:analysis; D009765:Obesity / Q000150:complications; D009852:Omentum / Q000276:immunology; D009928:Organ Specificity; D019707:Receptors, Chemokine / Q000032:analysis; D055607:Receptors, Natural Killer Cell / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017077:Culture Media, Conditioned; C508609:IL10 protein, human; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D019707:Receptors, Chemokine; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: cancer; inflammation; innate lymphocytes; obesity; omentum