How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?
How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?
Impaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response requires adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAs de novo and are dependent upon dietary intake for pre-formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (aLNA, 18:3n-3). We have shown that activation of peripheral blood mononuclear cells (PBMCs) increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the BBSRC responsive mode award ‘How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?’ is to determine how PUFA biosynthesis regulates T cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up-regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling.
Immune function, Healthy ageing, eicosanoids, epigenetics, polyunsaturated fatty acids, stable isotopes
350-355
Fielding, Barbara
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Calder, Philip
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Irvine, Nicola
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Miles, Elizabeth
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Lillycrop, Karen
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von Gerichten, Johanna
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Burdge, Graham
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1 December 2019
Fielding, Barbara
01e81be8-d62a-421e-a1c7-9191d7b5b7c5
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Irvine, Nicola
ed181be8-0435-49b7-bbc9-ddf2249fd2aa
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
von Gerichten, Johanna
fba4e87b-d6c7-4be0-92f8-54576c04458e
Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Fielding, Barbara, Calder, Philip, Irvine, Nicola, Miles, Elizabeth, Lillycrop, Karen, von Gerichten, Johanna and Burdge, Graham
(2019)
How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?
Nutrition Bulletin, 44 (4), .
(doi:10.1111/nbu.12404).
Abstract
Impaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response requires adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAs de novo and are dependent upon dietary intake for pre-formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (aLNA, 18:3n-3). We have shown that activation of peripheral blood mononuclear cells (PBMCs) increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the BBSRC responsive mode award ‘How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function?’ is to determine how PUFA biosynthesis regulates T cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up-regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling.
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How does polyunsaturated fatty acid biosynthesis regulate T lymphocyte function accepted
- Author's Original
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nbu.12404
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Accepted/In Press date: 4 September 2019
e-pub ahead of print date: 30 October 2019
Published date: 1 December 2019
Keywords:
Immune function, Healthy ageing, eicosanoids, epigenetics, polyunsaturated fatty acids, stable isotopes
Identifiers
Local EPrints ID: 435510
URI: http://eprints.soton.ac.uk/id/eprint/435510
ISSN: 1471-9827
PURE UUID: 1df58688-bd63-4513-b511-dcdb6fd7ca9f
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Date deposited: 08 Nov 2019 17:30
Last modified: 17 Mar 2024 02:42
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Author:
Barbara Fielding
Author:
Nicola Irvine
Author:
Johanna von Gerichten
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