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Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity
Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unkno...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686835/ https://www.ncbi.nlm.nih.gov/pubmed/37993715 http://dx.doi.org/10.1038/s41586-023-06749-3 |
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author | Fan, Hao Xia, Siyuan Xiang, Junhong Li, Yuancheng Ross, Matthew O. Lim, Seon Ah Yang, Fan Tu, Jiayi Xie, Lishi Dougherty, Urszula Zhang, Freya Q. Zheng, Zhong Zhang, Rukang Wu, Rong Dong, Lei Su, Rui Chen, Xiufen Althaus, Thomas Riedell, Peter A. Jonker, Patrick B. Muir, Alexander Lesinski, Gregory B. Rafiq, Sarwish Dhodapkar, Madhav V. Stock, Wendy Odenike, Olatoyosi Patel, Anand A. Opferman, Joseph Tsuji, Takemasa Matsuzaki, Junko Shah, Hardik Faubert, Brandon Elf, Shannon E. Layden, Brian Bissonnette, B. Marc He, Yu-Ying Kline, Justin Mao, Hui Odunsi, Kunle Gao, Xue Chi, Hongbo He, Chuan Chen, Jing |
author_facet | Fan, Hao Xia, Siyuan Xiang, Junhong Li, Yuancheng Ross, Matthew O. Lim, Seon Ah Yang, Fan Tu, Jiayi Xie, Lishi Dougherty, Urszula Zhang, Freya Q. Zheng, Zhong Zhang, Rukang Wu, Rong Dong, Lei Su, Rui Chen, Xiufen Althaus, Thomas Riedell, Peter A. Jonker, Patrick B. Muir, Alexander Lesinski, Gregory B. Rafiq, Sarwish Dhodapkar, Madhav V. Stock, Wendy Odenike, Olatoyosi Patel, Anand A. Opferman, Joseph Tsuji, Takemasa Matsuzaki, Junko Shah, Hardik Faubert, Brandon Elf, Shannon E. Layden, Brian Bissonnette, B. Marc He, Yu-Ying Kline, Justin Mao, Hui Odunsi, Kunle Gao, Xue Chi, Hongbo He, Chuan Chen, Jing |
author_sort | Fan, Hao |
collection | PubMed |
description | Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8(+) T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously(1). Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter(2,3), but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively(4,5). Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands(6–8). TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP–PKA–CREB axis for enhanced CD8(+) T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8(+) T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours. |
format | Online Article Text |
id | pubmed-10686835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106868352023-12-01 Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity Fan, Hao Xia, Siyuan Xiang, Junhong Li, Yuancheng Ross, Matthew O. Lim, Seon Ah Yang, Fan Tu, Jiayi Xie, Lishi Dougherty, Urszula Zhang, Freya Q. Zheng, Zhong Zhang, Rukang Wu, Rong Dong, Lei Su, Rui Chen, Xiufen Althaus, Thomas Riedell, Peter A. Jonker, Patrick B. Muir, Alexander Lesinski, Gregory B. Rafiq, Sarwish Dhodapkar, Madhav V. Stock, Wendy Odenike, Olatoyosi Patel, Anand A. Opferman, Joseph Tsuji, Takemasa Matsuzaki, Junko Shah, Hardik Faubert, Brandon Elf, Shannon E. Layden, Brian Bissonnette, B. Marc He, Yu-Ying Kline, Justin Mao, Hui Odunsi, Kunle Gao, Xue Chi, Hongbo He, Chuan Chen, Jing Nature Article Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8(+) T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously(1). Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter(2,3), but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively(4,5). Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands(6–8). TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP–PKA–CREB axis for enhanced CD8(+) T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8(+) T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours. Nature Publishing Group UK 2023-11-22 2023 /pmc/articles/PMC10686835/ /pubmed/37993715 http://dx.doi.org/10.1038/s41586-023-06749-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Fan, Hao Xia, Siyuan Xiang, Junhong Li, Yuancheng Ross, Matthew O. Lim, Seon Ah Yang, Fan Tu, Jiayi Xie, Lishi Dougherty, Urszula Zhang, Freya Q. Zheng, Zhong Zhang, Rukang Wu, Rong Dong, Lei Su, Rui Chen, Xiufen Althaus, Thomas Riedell, Peter A. Jonker, Patrick B. Muir, Alexander Lesinski, Gregory B. Rafiq, Sarwish Dhodapkar, Madhav V. Stock, Wendy Odenike, Olatoyosi Patel, Anand A. Opferman, Joseph Tsuji, Takemasa Matsuzaki, Junko Shah, Hardik Faubert, Brandon Elf, Shannon E. Layden, Brian Bissonnette, B. Marc He, Yu-Ying Kline, Justin Mao, Hui Odunsi, Kunle Gao, Xue Chi, Hongbo He, Chuan Chen, Jing Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title | Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title_full | Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title_fullStr | Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title_full_unstemmed | Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title_short | Trans-vaccenic acid reprograms CD8(+) T cells and anti-tumour immunity |
title_sort | trans-vaccenic acid reprograms cd8(+) t cells and anti-tumour immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686835/ https://www.ncbi.nlm.nih.gov/pubmed/37993715 http://dx.doi.org/10.1038/s41586-023-06749-3 |
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