美国哈佛医学院Francisco J. Quintana研究团队鉴定出促进肠道炎症的环境因素。该项研究成果于2022年10月20日在线发表在《自然》杂志上。

研究人员描述了一种综合的系统方法，通过结合公开的数据库、斑马鱼的化学筛选、机器学习和小鼠临床前模型来确定控制肠道炎症的环境因素。这种方法确定了除草剂丙炔酰胺会增加小肠和大肠的炎症。此外，结果表明，AHR-NF-κB-C/EBPβ信号轴在T细胞和树突状细胞中运作，促进肠道炎症，并被丙草胺作为靶标。总之，研究人员开发了一个管线，用于鉴定炎症性肠病（IBD）以及潜在的其他炎症性疾病的环境因素和发病机制。

据介绍，全基因组关联研究已经确定了与IBD（一种复杂的胃肠道慢性炎症性疾病）有关的风险位点。工业化国家IBD的发病率越来越高，而且在迁入疾病高发区的移民中观察到疾病风险增加，这表明环境因素也是决定IBD易感性和严重程度的重要因素。然而，由于缺乏系统调查的平台，与IBD相关的环境因素及其影响疾病的机制的识别一直受到阻碍。

附：英文原文

Title: Identification of environmental factors that promote intestinal inflammation

Author: Sanmarco, Liliana M., Chao, Chun-Cheih, Wang, Yu-Chao, Kenison, Jessica E., Li, Zhaorong, Rone, Joseph M., Rejano-Gordillo, Claudia M., Polonio, Carolina M., Gutierrez-Vazquez, Cristina, Piester, Gavin, Plasencia, Agustin, Li, Lucinda, Giovannoni, Federico, Lee, Hong-Gyun, Faust Akl, Camilo, Wheeler, Michael A., Mascanfroni, Ivan, Jaronen, Merja, Alsuwailm, Moneera, Hewson, Patrick, Yeste, Ada, Andersen, Brian M., Franks, Diana G., Huang, Chien-Jung, Ekwudo, Millicent, Tjon, Emily C., Rothhammer, Veit, Takenaka, Maisa, de Lima, Kalil Alves, Linnerbauer, Mathias, Guo, Lydia, Covacu, Ruxandra, Queva, Hugo, Fonseca-Castro, Pedro Henrique, Bladi, Maha Al, Cox, Laura M., Hodgetts, Kevin J., Hahn, Mark E., Mildner, Alexander, Korzenik, Joshua, Hauser, Russ, Snapper, Scott B., Quintana, Francisco J.

Issue&Volume: 2022-10-20

Abstract: Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)1—a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity2. However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR–NF-κB–C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases.

DOI: 10.1038/s41586-022-05308-6

Source: https://www.nature.com/articles/s41586-022-05308-6