Identification of environmental factors that promote intestinal inflammation

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B100
Abstract ID: 5401

Presenting Author:
Jessica E Kenison-White , Postdoctoral Research Fellow at Brigham and Women’s Hosp, Harvard Med. Sch.

Abstract:

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD)—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. To overcome this limitation, we developed an integrated systems approach which combines publicly available databases, zebrafish chemical screens, machine learning, and mouse preclinical models to identify environmental factors that control intestinal inflammation. Using this approach we established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we found 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.