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Retained NK Cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease
Natalie Stiglund1, Kristina Strand2,3, Martin Cornillet1
1Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Frontiers in Immunology
|June 20, 2019
Summary
Natural killer (NK) cells show minimal changes in non-alcoholic fatty liver disease (NAFLD) patients. The local tissue environment, not the disease itself, significantly alters NK cell characteristics in NAFLD and non-alcoholic steatohepatitis (NASH).
Area of Science:
- Immunology
- Hepatology
- Cell Biology
Background:
- Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are leading causes of chronic liver disease worldwide.
- Natural killer (NK) cells are implicated in NASH pathogenesis in animal models, but their role in human NASH is poorly understood.
- Investigating immune cell subsets, particularly NK cells, in human NAFLD is crucial for understanding disease mechanisms.
Purpose of the Study:
- To investigate disease-specific alterations in circulating and tissue-resident NK cells and other immune cells in patients with biopsy-confirmed NAFLD.
- To compare NK cell populations and their receptor expression in patients with NAFLD versus healthy controls.
- To assess the impact of the local microenvironment on NK cell populations in different tissues.
Main Methods:
- Utilized 18-color flow cytometry to analyze immune cell subsets in liver biopsy samples, adipose tissue, and peripheral blood from NAFLD patients and controls.
- Quantified NK cell numbers and assessed the expression of activating and inhibitory NK cell receptors.
- Evaluated NK cell differentiation and responsiveness to stimulation.
Main Results:
- Significant changes were observed in myeloid cell populations in NAFLD patients compared to controls.
- NK cell numbers were not altered in NAFLD patients.
- Minor differences in NK cell receptor expression were noted, except for increased NKG2D expression in NASH patients; however, NK cell function remained intact.
- Considerable differences in NK cell populations were found between liver, adipose tissue, and peripheral blood, independent of disease status.
Conclusions:
- Circulating NK cell numbers and function are largely preserved in human NAFLD/NASH.
- The local tissue microenvironment significantly shapes NK cell populations, irrespective of disease status.
- Further research is needed to understand the specific role of intrahepatic NK cells in NASH pathogenesis in humans.
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