Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, PA, USA.
Nat Commun. 2023 Nov 14;14(1):7363. doi: 10.1038/s41467-023-43211-4.
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.
环境因素是引发免疫紊乱的主要因素，如溃疡性结肠炎。然而，其具体身份仍不清楚。在这里，我们发现所消耗的 L-色氨酸（L-Trp）的量，一种普遍存在的饮食成分，决定了结肠 T 细胞归巢受体 GPR15 的转录水平，从而影响结肠 FOXP3 调节性 T（Treg）细胞的数量和局部免疫稳态。摄入的 L-Trp 被宿主 IDO1/2 酶而不是肠道微生物群转化为化合物，这些化合物通过芳香烃受体优先诱导 Treg 细胞中的 GPR15 转录。因此，两周的饮食 L-Trp 补充通过 GPR15 介导的归巢使结肠 GPR15 Treg 细胞增加近一倍，并显著降低未来发生结肠炎的风险。此外，人类每公斤体重消耗的 L-Trp 量比老鼠少 3-4 倍，而且结肠 GPR15 Treg 细胞也较少。因此，我们揭示了一种独立于微生物群的机制，将饮食 L-Trp 与结肠 Treg 细胞联系起来，这可能具有治疗潜力。
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