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Natural Killer Cells in Tissue Compartments

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01255

Retained NK cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease

Natalie Stiglund1,  Kristina Strand2, 3, Martin Cornillet4,  Per Stål5, 6, Anders Thorell7, 8, Christine Zimmer4, Erik Näslund7,  Silja Karlgren7,  Henrik Nilsson7, Gunnar Mellgren2, 3,  Johan A. Fernø2, 3, Hannes Hagström6, 9 and  Niklas K. Björkström4*
  • 1Center for Infectious Medicine, Department of Medicine, Huddinge, Karolinska Institutet, Sweden
  • 2Hormone Laboratory, Haukeland University Hospital, Norway
  • 3Mohn Nutrition Research Laboratory, Department of Clinical Science, Faculty of Medicine, University of Bergen, Norway
  • 4Karolinska Institute (KI), Sweden
  • 5Department of Upper GI Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden
  • 6Department of Medicine, Huddinge, Karolinska Institutet, Sweden
  • 7Department of Clinical Sciences, Danderyd Hospital, Sweden
  • 8Department of Surgery, Ersta Hospital, Sweden
  • 9Karolinska University Hospital, Sweden

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage nonalcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease. Here, we explored the presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD. Using 18-color-flow cytometry, substantial changes were observed in certain myeloid populations in patients as compared to controls. NK cell numbers, on the other hand, were not altered. Furthermore, only minor differences in expression of activating and inhibitory NK cell receptors were noted, with the exception of an increased expression of NKG2D on NK cells from patients with NASH. NK cell differentiation remained constant, and NK cells from these patients retain their ability to respond adequately upon stimulation. Instead, considerable alterations were observed between liver, adipose tissue, and peripheral blood NK cells, independently of disease status. Taken together, these results increase our understanding of the importance of the local microenvironment in shaping the NK cell compartment and stress the need for further studies exploring how NASH affects intrahepatic NK cells in humans.

Keywords: Natural Killer cells, NAFLD (non alcoholic fatty liver disease), Obesity, Adipose tissue immunology, liver immunology

Received: 03 Dec 2018; Accepted: 17 May 2019.

Edited by:

Michael A. Caligiuri, City of Hope National Medical Center, United States

Reviewed by:

Jacques Zimmer, Luxembourg Institute of Health (LIH), Luxembourg
Vincent Vieillard, Centre National de la Recherche Scientifique (CNRS), France  

Copyright: © 2019 Stiglund, Strand, Cornillet, Stål, Thorell, Zimmer, Näslund, Karlgren, Nilsson, Mellgren, Fernø, Hagström and Björkström. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Niklas K. Björkström, Karolinska Institute (KI), Solna, Sweden,