Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15

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 and Sangwon V. Kim ()
Additional contact information
Nguyen T. Van: Thomas Jefferson University
Karen Zhang: Thomas Jefferson University
Rachel M. Wigmore: Thomas Jefferson University
Anne I. Kennedy: Thomas Jefferson University
Carolina R. DaSilva: Thomas Jefferson University
Jialing Huang: Thomas Jefferson University
Manju Ambelil: Thomas Jefferson University
Jose H. Villagomez: Thomas Jefferson University
Gerald J. O’Connor: Thomas Jefferson University
Randy S. Longman: Jill Roberts Center for IBD, Weill Cornell Medicine
Miao Cao: Sidney Kimmel Medical College, Thomas Jefferson University
Adam E. Snook: Thomas Jefferson University
Michael Platten: German Cancer Research Center
Gerard Kasenty: Irving Medical Center
Luis J. Sigal: Thomas Jefferson University
George C. Prendergast: Sidney Kimmel Cancer Center, Jefferson Health
Sangwon V. Kim: Thomas Jefferson University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43211-4

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