Document Type

Article

Publication Date

11-14-2023

Comments

This article is the author's final published version in Nature Communications, Volume 14, Issue 1, 2023, Article number 7363.

The published version is available at https://doi.org/10.1038/s41467-023-43211-4.

Copyright © The Author(s) 2023

Abstract

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary Information.pdf (1189 kB)
Peer Review File.pdf (493 kB)
Reporting Summary.pdf (347 kB)
Source Data.xlsx (130 kB)

PubMed ID

37963876

Language

English

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