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Title: Remodelling of primary human CD4+ T cell plasma membrane order by n-3 PUFA.

Authors: Fan, Yang-Yi; Fuentes, Natividad R; Hou, Tim Y; Barhoumi, Rola; Li, Xian C; Deutz, Nicolaas E P; Engelen, Marielle P K J; McMurray, David N; Chapkin, Robert S

Published In Br J Nutr, (2018 Jan)

Abstract: Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.

PubMed ID: 29249211 Exiting the NIEHS site

MeSH Terms: Aged; Aged, 80 and over; CD4-Positive T-Lymphocytes/immunology*; CD4-Positive T-Lymphocytes/ultrastructure*; Cell Membrane/chemistry; Cell Membrane/drug effects*; Cell Membrane/physiology; Dietary Fats/administration & dosage; Dietary Supplements; Eicosapentaenoic Acid/blood; Energy Metabolism/drug effects; Fatty Acids, Omega-3/pharmacology*; Fatty Acids/blood; Female; Fish Oils/administration & dosage; Humans; Lymphocyte Activation/drug effects; Male; Membrane Lipids/blood; Membrane Lipids/chemistry; Middle Aged; Mitochondria/drug effects; Mitochondria/metabolism; Phospholipids/blood; Phospholipids/chemistry; Pilot Projects

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