Cargando…
Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15
Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645889/ https://www.ncbi.nlm.nih.gov/pubmed/37963876 http://dx.doi.org/10.1038/s41467-023-43211-4 |
_version_ | 1785147416789385216 |
---|---|
author | Van, Nguyen T. Zhang, Karen Wigmore, Rachel M. Kennedy, Anne I. DaSilva, Carolina R. Huang, Jialing Ambelil, Manju Villagomez, Jose H. O’Connor, Gerald J. Longman, Randy S. Cao, Miao Snook, Adam E. Platten, Michael Kasenty, Gerard Sigal, Luis J. Prendergast, George C. Kim, Sangwon V. |
author_facet | Van, Nguyen T. Zhang, Karen Wigmore, Rachel M. Kennedy, Anne I. DaSilva, Carolina R. Huang, Jialing Ambelil, Manju Villagomez, Jose H. O’Connor, Gerald J. Longman, Randy S. Cao, Miao Snook, Adam E. Platten, Michael Kasenty, Gerard Sigal, Luis J. Prendergast, George C. Kim, Sangwon V. |
author_sort | Van, Nguyen T. |
collection | PubMed |
description | Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3(+) regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15(+) Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3–4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15(+) Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential. |
format | Online Article Text |
id | pubmed-10645889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106458892023-11-14 Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 Van, Nguyen T. Zhang, Karen Wigmore, Rachel M. Kennedy, Anne I. DaSilva, Carolina R. Huang, Jialing Ambelil, Manju Villagomez, Jose H. O’Connor, Gerald J. Longman, Randy S. Cao, Miao Snook, Adam E. Platten, Michael Kasenty, Gerard Sigal, Luis J. Prendergast, George C. Kim, Sangwon V. Nat Commun Article Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3(+) regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15(+) Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3–4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15(+) Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential. Nature Publishing Group UK 2023-11-14 /pmc/articles/PMC10645889/ /pubmed/37963876 http://dx.doi.org/10.1038/s41467-023-43211-4 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Van, Nguyen T. Zhang, Karen Wigmore, Rachel M. Kennedy, Anne I. DaSilva, Carolina R. Huang, Jialing Ambelil, Manju Villagomez, Jose H. O’Connor, Gerald J. Longman, Randy S. Cao, Miao Snook, Adam E. Platten, Michael Kasenty, Gerard Sigal, Luis J. Prendergast, George C. Kim, Sangwon V. Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title | Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title_full | Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title_fullStr | Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title_full_unstemmed | Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title_short | Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 |
title_sort | dietary l-tryptophan consumption determines the number of colonic regulatory t cells and susceptibility to colitis via gpr15 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645889/ https://www.ncbi.nlm.nih.gov/pubmed/37963876 http://dx.doi.org/10.1038/s41467-023-43211-4 |
work_keys_str_mv | AT vannguyent dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT zhangkaren dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT wigmorerachelm dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT kennedyannei dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT dasilvacarolinar dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT huangjialing dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT ambelilmanju dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT villagomezjoseh dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT oconnorgeraldj dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT longmanrandys dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT caomiao dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT snookadame dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT plattenmichael dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT kasentygerard dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT sigalluisj dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT prendergastgeorgec dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 AT kimsangwonv dietaryltryptophanconsumptiondeterminesthenumberofcolonicregulatorytcellsandsusceptibilitytocolitisviagpr15 |