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: Melissa J Conroy, Vivienne Fitzgerald, Suzanne L Doyle, Shauna Channon, Zivile Useckaite, Niamh Gilmartin, Cliona O'Farrelly, Narayanasamy Ravi, John V Reynolds, Joanne Lysaght
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 100 Issue 6 Pg. 1435-1442 (12 2016) ISSN: 1938-3673 [Electronic] England
• PMID: 27365528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Society for Leukocyte Biology.

Chemical References

• Culture Media, Conditioned
• IL10 protein, human
• NCR1 protein, human
• Natural Cytotoxicity Triggering Receptor 1
• Receptors, Chemokine
• Receptors, Natural Killer Cell
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Adenocarcinoma (blood, etiology, immunology)
• Aged
• Cell Survival
• Cells, Cultured
• Cellular Microenvironment
• Chemotaxis
• Culture Media, Conditioned (pharmacology)
• Cytotoxicity, Immunologic
• Esophageal Neoplasms (blood, etiology, immunology)
• Female
• Humans
• Interleukin-10 (biosynthesis)
• Intra-Abdominal Fat (immunology)
• Killer Cells, Natural (immunology)
• Liver (immunology)
• Male
• Middle Aged
• Natural Cytotoxicity Triggering Receptor 1 (analysis)
• Obesity (complications)
• Omentum (immunology)
• Organ Specificity
• Receptors, Chemokine (analysis)
• Receptors, Natural Killer Cell (analysis)
• Tumor Necrosis Factor-alpha (biosynthesis)