Main author: Kirstine Nolling Jensen
Institution or Company: Faculty of Medicine, Biomedical Center, University of Iceland and Department of Immunology, Landspitali – the National University Hospital Iceland
Co-Authors, Institution or Company:
Sara Rut Bjorgvinsdottir, Faculty of Medicine, Biomedical Center, University of Iceland and Department of Immunology, Landspitali – the National University Hospital Iceland. Sigridur Eyglo Unnarsdottir, Department of Immunology, Landspitali – the National University Hospital Iceland and Faculty of Pharmaceutical Sciences, University of Iceland. Jona Freysdottir, Faculty of Medicine, Biomedical Center, University of Iceland and Department of Immunology, Landspitali – the National University Hospital Iceland. Ingibjorg Hardardottir, Faculty of Medicine, Biomedical Center, University of Iceland and Department of Immunology, Landspitali – the National University Hospital Iceland.
Introduction: Our previous results indicate that NK cells are indispensable for resolution of antigen-induced inflammation. They also show that dietary fish oil (Fo) induces recruitment of NK cells to the inflamed site and enhances resolution of inflammation. In this study we further characterized the effects of Fo on NK cells and resolution of inflammation.
Methods: Mice were fed control or Fo diets, immunized with mBSA, challenged intraperitoneally with mBSA, sacrificed and mesenteric lymph nodes and peritoneal lavage collected. Peritoneal cell expression of surface molecules was determined by flow cytometry, cytokine concentrations by Luminex, apoptosis by TUNEL staining, and RNA of sorted NK cells sequenced.
Results: Fo induced peritoneal recruitment of differentiated NK cells expressing high levels of CCR5, TRAIL, NKp46, and CD107a. NK cells in Fo mice showed enrichment of the JAK/STAT pathway and several migration markers. Fo induced higher peritoneal concentrations of CCL5 and CXCL12, reduced IL-6 levels, but increased concentration of soluble TNFRII substantially. Higher numbers of apoptotic cells were detected in draining lymph nodes of Fo mice.
Conclusion: Dietary Fo may induce recruitment of differentiated NK cells to the inflamed site through increased production of CCL5 and CXCL12. Its induction of NK cell expression of the cytotoxic receptor NKp46 and other activation molecules may lead to increased NK cell-induced apoptosis of neutrophils. This may induce shedding of TNFRII from neutrophils and neutralization of pro-inflammatory TNF, thus, leading to enhanced resolution of inflammation. Further studies will aim to establish how NK cells act as pro-resolution effector cells.
