Dietary Fish Oil Increases the Number of CD11b+CD27- NK Cells at the Inflammatory Site and Enhances Key Hallmarks of Resolution of Murine Antigen-Induced Peritonitis

Kirstine Nolling Jensen; Marieke Heijink; Martin Giera; Jona Freysdottir; Ingibjorg Hardardottir

doi:10.2147/JIR.S342399

Dietary Fish Oil Increases the Number of CD11b⁺CD27^- NK Cells at the Inflammatory Site and Enhances Key Hallmarks of Resolution of Murine Antigen-Induced Peritonitis

J Inflamm Res. 2022 Jan 14:15:311-324. doi: 10.2147/JIR.S342399. eCollection 2022.

Authors

Kirstine Nolling Jensen^{1

2}, Marieke Heijink³, Martin Giera³, Jona Freysdottir^#^{1

2}, Ingibjorg Hardardottir^#^{1

2}

Affiliations

¹ Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland.
² Department of Immunology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
³ Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.

^# Contributed equally.

Abstract

Purpose: To determine the effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on recruitment of natural killer (NK) cells and resolution responses in antigen-induced peritonitis in mice.

Methods: Mice were fed fish oil-enriched or control diets, immunized twice and challenged intraperitoneally with methylated bovine serum albumin. Prior to and at different time-points following inflammation induction, expression of surface molecules on peritoneal cells was determined by flow cytometry, concentration of soluble mediators in peritoneal fluid by ELISA or Luminex, and of lipid mediators by LC-MS/MS, and number of apoptotic cells in mesenteric lymph nodes by TUNEL staining.

Results: Mice fed the fish oil diet had higher number of CD11b⁺CD27^- NK cells as well as a higher proportion of CD107a⁺ NK cells in their peritoneum 6 h after inflammation induction than mice fed the control diet. They also had higher numbers of CCR5⁺ NK cells and higher concentrations of CCL5 and CXCL12. Additionally, a higher fraction of apoptotic neutrophils but lower fraction of CD47⁺ neutrophils were present in the peritoneum of mice fed the fish oil diet 6 h after inflammation induction and the fish oil fed mice had a shorter resolution interval. They also had lower concentrations of pro-inflammatory mediators but higher concentrations of the anti-inflammatory/pro-resolution mediators TGF-β, IGF-1, and soluble TNF RII, as well as higher ratios of hydroxyeicosapentaenoic acid (HEPE) to hydroxyeicosatetraenoic acid (HETE) than mice fed the control diet.

Conclusion: The results demonstrate that dietary fish oil increases the number of mature NK cells at the inflamed site in antigen-induced peritonitis and enhances several key hallmarks of resolution of inflammation, casting light on the potential mechanisms involved.

Keywords: apoptosis; lipid mediators; natural killer cells; neutrophils.

Grants and funding

This study was funded by the Icelandic Research Fund (# 173973051), The University of Iceland Research Fund (both project and doctoral), Landspitali University Hospital Research Fund, and the Memorial Fund of Helga Jonsdottir and Sigurlidi Kristjansson.