Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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
_version_ 1785151850445537280
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
work_keys_str_mv AT fanhao transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT xiasiyuan transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT xiangjunhong transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT liyuancheng transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT rossmatthewo transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT limseonah transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT yangfan transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT tujiayi transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT xielishi transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT doughertyurszula transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT zhangfreyaq transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT zhengzhong transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT zhangrukang transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT wurong transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT donglei transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT surui transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT chenxiufen transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT althausthomas transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT riedellpetera transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT jonkerpatrickb transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT muiralexander transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT lesinskigregoryb transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT rafiqsarwish transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT dhodapkarmadhavv transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT stockwendy transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT odenikeolatoyosi transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT patelananda transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT opfermanjoseph transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT tsujitakemasa transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT matsuzakijunko transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT shahhardik transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT faubertbrandon transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT elfshannone transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT laydenbrian transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT bissonnettebmarc transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT heyuying transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT klinejustin transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT maohui transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT odunsikunle transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT gaoxue transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT chihongbo transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT hechuan transvaccenicacidreprogramscd8tcellsandantitumourimmunity
AT chenjing transvaccenicacidreprogramscd8tcellsandantitumourimmunity