FOXP3型
免疫系统
芳香烃受体
结肠炎
肠道菌群
受体
转录因子
生物
微生物群
化学
免疫学
生物信息学
生物化学
基因
作者
Nguyễn Thị Thuỳ Vân,Karen Zhang,Rachel M. Wigmore,A. Kennedy,Carolina R. Melo‐Silva,Jialing Huang,Manju Ambelil,Jose H. Villagomez,Gail O'Connor,Randy S. Longman,Miao Cao,Adam E. Snook,Michael Platten,Gerard Kasenty,Luis J. Sigal,George C. Prendergast,Sangwon V. Kim
标识
DOI:10.1038/s41467-023-43211-4
摘要
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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