The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function

Journal of Leukocyte Biology

Vivienne Fitzgerald²  John V. Reynolds, and¹  Zivile Useckaite²  Niamh Gilmartin²  Melissa J. Conroy²  Cliona O™Farrelly⁵  Shauna Channon²  Joanne Lysaght²  Narayanasamy Ravi⁴  Suzanne L. Doyle³ 

[1]Department of Surgery, Trinity Translational Medicine Institute, St. James™s Hospital, Trinity College Dublin, Ireland

[2] Gastro-intestinal Medicine and Surgery, St. James™s Hospital, Dublin, Ireland

[3]Department of Surgery, Trinity Translational Medicine Institute, St. James™s Hospital, Trinity College Dublin, Ireland

[4] School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland

[5]Gastro-intestinal Medicine and Surgery, St. James™s Hospital, Dublin, Ireland

[6]Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland Department of Surgery, Trinity Translational Medicine Institute, St. James™s Hospital, Trinity College Dublin, Ireland

关键词: inflammation;    omentum;    cancer;    obesity;    innate lymphocytes;   

DOI  :  10.1189/jlb.5AB1115-493RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown