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Identification of environmental factors that promote intestinal inflammation

Item Type:Article
Title:Identification of environmental factors that promote intestinal inflammation
Creators Name:Sanmarco, L.M. and Chao, C.C. and Wang, Y.C. and Kenison, J.E. and Li, Z. and Rone, J.M. and Rejano-Gordillo, C.M. and Polonio, C.M. and Gutierrez-Vazquez, C. and Piester, G. and Plasencia, A. and Li, L. and Giovannoni, F. and Lee, H.G. and Faust Akl, C. and Wheeler, M.A. and Mascanfroni, I. and Jaronen, M. and Alsuwailm, M. and Hewson, P. and Yeste, A. and Andersen, B.M. and Franks, D.G. and Huang, C.J. and Ekwudo, M. and Tjon, E.C. and Rothhammer, V. and Takenaka, M. and de Lima, K.A. and Linnerbauer, M. and Guo, L. and Covacu, R. and Queva, H. and Fonseca-Castro, P.H. and Bladi, M.A. and Cox, L.M. and Hodgetts, K.J. and Hahn, M.E. and Mildner, A. and Korzenik, J. and Hauser, R. and Snapper, S.B. and Quintana, F.J.
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 severity. 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.
Keywords:Crohn Disease, Genome-Wide Association Study, Inflammation, Inflammatory Bowel Diseases, Animals, Mice, Zebrafish
Publisher:Nature Publishing Group
Page Range:801-809
Date:24 November 2022
Additional Information:Copyright © 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Official Publication:https://doi.org/10.1038/s41586-022-05308-6
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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