Identification of environmental factors that promote intestinal inflammation

Author(s):Show less -

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 ; Akl, Camilo Faust ; 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 ; Al Bladi, Maha ; Cox, Laura M. ; Hodgetts, Kevin J. ; Hahn, Mark E. ; Mildner, Alexander ; Korzenik, Joshua ; Hauser, Russ ; Snapper, Scott B. ; Quintana, Francisco J.

• Document type: Journal article
• Source: Nature; v. 611, n. 7937, p. 38-pg., 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 severity(2). 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 modelsto identify environmental factorsthat 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-kappa B-C/EBP beta signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline forthe identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases. (AU)

• FAPESP's process: 19/13731-0 - MicroRNAs, neurodevelopment and antiviral immune response: how they can be connected?
• Grantee: Carolina Manganeli Polonio
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate