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.
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Authors | Nguyen T Van, Karen Zhang, Rachel M Wigmore, Anne I Kennedy, Carolina R DaSilva, Jialing Huang, Manju Ambelil, Jose H Villagomez, Gerald J O'Connor, Randy S Longman, Miao Cao, Adam E Snook, Michael Platten, Gerard Kasenty, Luis J Sigal, George C Prendergast, Sangwon V Kim |
Journal | Nature communications
(Nat Commun)
Vol. 14
Issue 1
Pg. 7363
(11 14 2023)
ISSN: 2041-1723 [Electronic] England |
PMID | 37963876
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2023. The Author(s). |
Chemical References |
- Tryptophan
- GPR15 protein, human
- Receptors, Peptide
- Receptors, G-Protein-Coupled
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Topics |
- Humans
- Mice
- Animals
- T-Lymphocytes, Regulatory
- Tryptophan
- Colitis
(chemically induced)
- Colon
- Colitis, Ulcerative
- Receptors, Peptide
- Receptors, G-Protein-Coupled
(genetics)
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