Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3+ T lymphocytes
Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3+ T lymphocytes
Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course. We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3+ T lymphocytes and in CD3+ T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and ω-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [13C]18:3ω-3 were constitutive hydroxyoctadecatrienoic acid synthesis and β-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain ω-3 PUFA synthesis was a relatively minor metabolic fate of 18:3ω-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors. Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.
1-13
West, Annette Lucy
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von Gerichten, Johanna
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Irvine, Nicola Alice
ed181be8-0435-49b7-bbc9-ddf2249fd2aa
Miles, Elizabeth
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Lillycrop, Karen
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Calder, Philip
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Fielding, Barbara
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Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
13 December 2022
West, Annette Lucy
e8dacc1a-5fdc-4a4f-92d8-608f2ea2994c
von Gerichten, Johanna
98e28a66-a955-4c82-9930-8bd0efa3f8f4
Irvine, Nicola Alice
ed181be8-0435-49b7-bbc9-ddf2249fd2aa
Miles, Elizabeth
20332899-ecdb-4214-95bc-922dde36d416
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Calder, Philip
1797e54f-378e-4dcb-80a4-3e30018f07a6
Fielding, Barbara
0413ec53-346a-4b4d-adaa-e7767e79e6d2
Burdge, Graham
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
West, Annette Lucy, von Gerichten, Johanna, Irvine, Nicola Alice, Miles, Elizabeth, Lillycrop, Karen, Calder, Philip, Fielding, Barbara and Burdge, Graham
(2022)
Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3+ T lymphocytes.
Frontiers in Immunology, .
(doi:10.3389/fimmu.2022.1079642).
Abstract
Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course. We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3+ T lymphocytes and in CD3+ T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and ω-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [13C]18:3ω-3 were constitutive hydroxyoctadecatrienoic acid synthesis and β-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain ω-3 PUFA synthesis was a relatively minor metabolic fate of 18:3ω-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors. Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.
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West Front Immunol Submiitted w_o EN Oct 2022
- Accepted Manuscript
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fimmu-13-1079642
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Accepted/In Press date: 23 November 2022
Published date: 13 December 2022
Identifiers
Local EPrints ID: 473459
URI: http://eprints.soton.ac.uk/id/eprint/473459
ISSN: 1664-3224
PURE UUID: 99bc75f1-40bb-414b-bdbd-5afc13cf2c7e
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Date deposited: 19 Jan 2023 17:33
Last modified: 17 Mar 2024 02:42
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Author:
Annette Lucy West
Author:
Johanna von Gerichten
Author:
Nicola Alice Irvine
Author:
Barbara Fielding
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