Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15
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 leve...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43211-4 |
| _version_ | 1797558113238253568 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nguyen T. Van |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:25:51Z |
| format | Article |
| id | doaj.art-ec2a535921bc46a180d596010b048d5b |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:25:51Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-ec2a535921bc46a180d596010b048d5b2023-11-20T10:11:18ZengNature PortfolioNature Communications2041-17232023-11-0114111510.1038/s41467-023-43211-4Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15Nguyen T. Van0Karen Zhang1Rachel M. Wigmore2Anne I. Kennedy3Carolina R. DaSilva4Jialing Huang5Manju Ambelil6Jose H. Villagomez7Gerald J. O’Connor8Randy S. Longman9Miao Cao10Adam E. Snook11Michael Platten12Gerard Kasenty13Luis J. Sigal14George C. Prendergast15Sangwon V. Kim16Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Pathology, Anatomy, & Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Pathology, Anatomy, & Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityJill Roberts Center for IBD, Weill Cornell MedicineDepartment of Pharmacology, Physiology, & Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityCCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research CenterDepartment of Genetics and Development, Irving Medical CenterDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversitySidney Kimmel Cancer Center, Jefferson HealthDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson UniversityAbstract 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.https://doi.org/10.1038/s41467-023-43211-4 |
| spellingShingle | 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 Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15 Nature Communications |
| 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 |
| url | https://doi.org/10.1038/s41467-023-43211-4 |
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