한빛사논문
- 조회167
Nguyen T. Van 1,2,12, Karen Zhang 1,2,12, Rachel M. Wigmore 1,2, Anne I. Kennedy 1,2, Carolina R. DaSilva 1,2, Jialing Huang 3,11, Manju Ambelil 3, Jose H. Villagomez 1,2, Gerald J. O’Connor 1,2, Randy S. Longman 4, Miao Cao 5, Adam E. Snook 1,2,5, Michael Platten 6,7,8, Gerard Kasenty 9, Luis J. Sigal 1,2, George C. Prendergast 2,10 & Sangwon V. Kim 1,2,*
1Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
2Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, PA, USA.
3Department of Pathology, Anatomy, & Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
4Jill Roberts Center for IBD, Weill Cornell Medicine, New York, NY, USA.
5Department of Pharmacology, Physiology, & Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
6CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.
7Department of Neurology, Medical Faculty Mannheim, MCTN, Heidelberg University, Heidelberg, Germany.
8DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
9Department of Genetics and Development, Irving Medical Center, Columbia University, NY, USA.
10Lankenau Institute of Medical Research, Wynnewood, PA, USA.
11Present address:Anatomic Pathology, Geisinger Medical Center, Danville, PA, USA.
12These authors contributed equally: Nguyen T. Van, Karen Zhang.
*Corresponding author: correspondence to Sangwon V. Kim
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.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-27)
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
