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

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

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)163-175
Number of pages13
JournalBritish Journal of Nutrition
Volume119
Issue number2
DOIs
StatePublished - Jan 28 2018

Keywords

  • CD4 T cells
  • Generalised polarisation
  • Giant plasma membrane vesicles
  • Phase separation
  • n-3 PUFA

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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