Identification of environmental factors that promote intestinal inflammation.

Sanmarco LM, Chao CC, Wang YC, Kenison JE, Li Z, Rone JM, Rejano-Gordillo CM, Polonio CM, Gutierrez-Vazquez C, Piester G, Plasencia A, Li L, Giovannoni F, Lee HG, Akl CF, Wheeler MA, Mascanfroni I, Jaronen M, Alsuwailm M, Hewson P, Yeste A, Andersen BM, Franks DG, Huang CJ, Ekwudo M, Tjon EC, Rothhammer V, Takenaka M, De Lima KA, Linnerbauer M, Guo L, Covacu R, Queva H, Fonseca-Castro PH, Al Bladi M, Cox LM, Hodgetts KJ, Hahn ME, Mildner A, Korzenik J, Hauser R, Snapper SB, Quintana FJ (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nature Nature Research

Book Volume: 611

Pages Range: 801-809

Journal Issue: 7937

DOI: 10.1038/s41586-022-05308-6

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.

Authors with CRIS profile

Veit Rothhammer

Involved external institutions

Harvard University US United States (USA) (US) National Yang Ming Chiao Tung University TW Taiwan (TW) Woods Hole Oceanographic Institute US United States (USA) (US) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Boston Children's Hospital US United States (USA) (US)

How to cite

APA:

Sanmarco, L.M., Chao, C.-C., Wang, Y.-C., Kenison, J.E., Li, Z., Rone, J.M.,... Quintana, F.J. (2022). Identification of environmental factors that promote intestinal inflammation. Nature, 611(7937), 801-809. https://doi.org/10.1038/s41586-022-05308-6

MLA:

Sanmarco, Liliana M., et al. "Identification of environmental factors that promote intestinal inflammation." Nature 611.7937 (2022): 801-809.

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