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

  • Yang-Yi Fan (a1), Natividad R. Fuentes (a1) (a2), Tim Y. Hou (a1), Rola Barhoumi (a1) (a3), Xian C. Li (a4), Nicolaas E. P. Deutz (a5) (a6), Marielle P. K. J. Engelen (a5) (a6), David N. McMurray (a1) (a7) and Robert S. Chapkin (a1) (a2) (a6)...

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.

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Corresponding author

* Corresponding author: Dr R. S. Chapkin, fax +1 979 458 3704, email r-chapkin@tamu.edu

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Present address: Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics and Gynecology, University of Texas SouthWestern Medical Center, Dallas, TX 75390, USA.

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