Identification of environmental factors that promote intestinal inflammation

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

*此作品的通信作者

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

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.

原文English
期刊Nature
DOIs
出版狀態Accepted/In press - 2022

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