TY - JOUR
T1 - The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function
AU - Conroy, Melissa J.
AU - Fitzgerald, Vivienne
AU - Doyle, Suzanne L.
AU - Channon, Shauna
AU - Useckaite, Zivile
AU - Gilmartin, Niamh
AU - O’Farrelly, Cliona
AU - Ravi, Narayanasamy
AU - Reynolds, John V.
AU - Lysaght, Joanne
PY - 2016/12
Y1 - 2016/12
N2 - 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 antiinflammatory homeostatic role.
AB - 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 antiinflammatory homeostatic role.
KW - Cancer
KW - Inflammation
KW - Innate lymphocytes
KW - Obesity
KW - Omentum
UR - http://www.scopus.com/inward/record.url?scp=85003037438&partnerID=8YFLogxK
U2 - 10.1189/jlb.5AB1115-493RR
DO - 10.1189/jlb.5AB1115-493RR
M3 - Comment/debate
C2 - 27365528
AN - SCOPUS:85003037438
SN - 0741-5400
VL - 100
SP - 1435
EP - 1442
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -