英国伦敦帝国理工学院Chris Schiering、Benjamin G. Wiggins团队取得一项新突破。他们的研究发现芳香烃受体（AHR）配体的内皮传感调节肠道稳态。这一研究成果发表在2023年8月16日出版的国际学术期刊《自然》上。

研究人员发现AHR是成年小鼠和人原代内皮细胞中膳食代谢物EC感应的关键因子。研究人员首先得到了小鼠小肠内皮细胞的单细胞图谱，揭示了血液和淋巴EC的细胞复杂性和功能异质性。对单细胞水平AHR介导的反应确定了组织保护性转录特征和调节网络，促进稳态时细胞的静止和血管的正常功能。成年小鼠内皮AHR缺失会导致炎症反应失调，并启动增殖途径。

此外，需要内皮感知膳食AHR配体以达到防止肠道感染的最佳效果。在人类EC中，AHR信号传导促进静息并抑制炎症介质的激活。总之，该研究数据全面剖析了环境传感对肠内皮的影响，表明内皮AHR信号可整合膳食因素，通过促进EC静息和血管正常来维持组织稳态。

据介绍，内皮细胞存在于血液和淋巴脉管系统中，是重要的物理屏障，控制营养物质的运输、促进组织免疫监测并协调血管/淋巴管生成。在肠道中，饮食和微生物在调节器官稳态中尤为重要。然而，目前尚不清楚肠道EC是否主动感知和整合这些信号。

附：英文原文

Title: Endothelial sensing of AHR ligands regulates intestinal homeostasis

Author: Wiggins, Benjamin G., Wang, Yi-Fang, Burke, Alice, Grunberg, Nil, Vlachaki Walker, Julia M., Dore, Marian, Chahrour, Catherine, Pennycook, Betheney R., Sanchez-Garrido, Julia, Vernia, Santiago, Barr, Alexis R., Frankel, Gad, Birdsey, Graeme M., Randi, Anna M., Schiering, Chris

Issue&Volume: 2023-08-16

Abstract: Endothelial cells (ECs) line the blood and lymphatic vasculature, and act as an essential physical barrier, control nutrient transport, facilitate tissue immunosurveillance, and coordinate angiogenesis/ lymphangiogenesis1,2. In the intestine, dietary and microbial cues are particularly important in the regulation of organ homeostasis. However, whether enteric ECs actively sense and integrate such signals is currently unknown. Here, we show that the aryl hydrocarbon receptor (AHR) acts as a critical node for EC-sensing of dietary metabolites in adult mice and human primary ECs. We first established a comprehensive single-cell endothelial atlas of the mouse small intestine, uncovering the cellular complexity and functional heterogeneity of blood and lymphatic ECs. Analyses of AHR mediated responses at single-cell resolution identified tissue-protective transcriptional signatures and regulatory networks promoting cellular quiescence and vascular normalcy at steady state. Endothelial AHR-deficiency in adult mice resulted in dysregulated inflammatory responses, and the initiation of proliferative pathways. Furthermore, endothelial sensing of dietary AHR ligands was required for optimal protection against enteric infection. In human ECs, AHR signalling promoted quiescence and restrained activation by inflammatory mediators. Together, our data provide a comprehensive dissection of the impact of environmental sensing across the spectrum of enteric endothelia, demonstrating that endothelial AHR signalling integrates dietary cues to maintain tissue homeostasis by promoting EC quiescence and vascular normalcy.

DOI: 10.1038/s41586-023-06508-4

Source: https://www.nature.com/articles/s41586-023-06508-4