Aryl hydrocarbon receptor (AHR) signalling integrates biological processes that sense and respond to environmental, dietary, and metabolic challenges to ensure tissue homeostasis. AHR is a transcription factor that is inactive in the cytosol but upon encounter with ligand translocates to the nucleus and drives the expression of AHR targets, including genes of the cytochrome P4501 family of enzymes such as Cyp1a1. To dynamically visualise AHR activity in vivo, we generated reporter mice in which firefly luciferase (Fluc) was non-disruptively targeted into the endogenous Cyp1a1 locus. Exposure of these animals to FICZ, 3-MC or to dietary I3C induced strong bioluminescence signal and Cyp1a1 expression in many organs including liver, lung and intestine. Longitudinal studies revealed that AHR activity was surprisingly long-lived in the lung, with sustained Cyp1a1 expression evident in discrete populations of cells including columnar epithelia around bronchioles. Our data link diet to lung physiology and also reveal the power of bespoke Cyp1a1-Fluc reporters to longitudinally monitor AHR activity in vivo.

芳基碳氢化合物受体 (AHR) 信号传导整合了感知和响应环境、饮食和代谢挑战的生物过程，以确保组织稳态。 AHR 是一种转录因子，在细胞质中不活跃，但在遇到配体时易位到细胞核并驱动 AHR 靶标的表达，包括细胞色素 P4501 酶家族的基因，例如Cyp1a1。为了动态可视化体内 AHR 活性，我们生成了报告小鼠，其中萤火虫荧光素酶 ( Fluc ) 非破坏性地靶向内源性Cyp1a1基因座。将这些动物暴露于 FICZ、3-MC 或饮食 I3C 会诱导强烈的生物发光信号，并在许多器官（包括肝、肺和肠）中表达Cyp1a1 。纵向研究表明，AHR 活性在肺中的寿命令人惊讶，在包括细支气管周围柱状上皮在内的离散细胞群中，Cyp1a1持续表达明显。我们的数据将饮食与肺生理学联系起来，并揭示了定制的Cyp1a1-Fluc记者纵向监测体内 AHR 活动的能力。