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

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Listed:
  • Nguyen T. Van

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Karen Zhang

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Rachel M. Wigmore

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Anne I. Kennedy

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Carolina R. DaSilva

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Jialing Huang

    (Thomas Jefferson University
    Geisinger Medical Center)

  • Manju Ambelil

    (Thomas Jefferson University)

  • Jose H. Villagomez

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • Gerald J. O’Connor

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • 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
    Sidney Kimmel Cancer Center, Jefferson Health
    Sidney Kimmel Medical College, Thomas Jefferson University)

  • Michael Platten

    (German Cancer Research Center
    Medical Faculty Mannheim, MCTN, Heidelberg University
    DKFZ Hector Cancer Institute at the University Medical Center Mannheim)

  • Gerard Kasenty

    (Irving Medical Center)

  • Luis J. Sigal

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

  • George C. Prendergast

    (Sidney Kimmel Cancer Center, Jefferson Health
    Lankenau Institute of Medical Research)

  • Sangwon V. Kim

    (Thomas Jefferson University
    Sidney Kimmel Cancer Center, Jefferson Health)

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.

Suggested Citation

  • 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, 2023. "Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43211-4
    DOI: 10.1038/s41467-023-43211-4
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