Article Text
Statistics from Altmetric.com
Basic science
A systematic pipeline for investigating environmental factors in inflammatory bowel disease
Sanmarco L, Chao C, Wang Y, et al. Identification of environmental factors that promote intestinal inflammation. Nature 2022; doi: 10.1038/s41586-022-05308-6.
Environmental factors have been implicated in the development of inflammatory bowel diseases (IBD). Mechanistic studies have been limited by the lack of systematic investigation. In this study, Sanmarco et al demonstrated a platform whereby known IBD genetic risk loci, high throughput toxicology and small-molecule zebrafish screens were used in combination with a trinitrobenzene sulfonic acid (TNBS)-induced colitis mouse model. First using the Toxicity Forecaster (ToxCast) database, they identified environmental chemicals found to be active in bioassays associated with known proinflammatory IBD pathways such as aryl hydrocarbon receptor (AHR) signalling. Then, using predictive machine learning methods, further chemicals were identified that worsen intestinal inflammation. Furthermore, these were ranked using an algorithm and validated in zebrafish at different doses. From these, propyzamide (a commonly used herbicide on crops) was selected for follow-up studies. In zebrafish, propyzamide did not induce colitis without TNBS. However, with the addition of TNBS, it did worsen TNBS-induced colitis, as evidenced in a mouse model by colon shortening, weight loss and histological evaluation, as well as inducing an ileal and caecal dysbiosis. RNA-sequencing (RNA-seq) analysis indicated upregulation of the pro-inflammatory pathways for nuclear factor-κB (NF-κB) activation and integrin signalling. Single-cell RNA-seq of colons in mice treated with propyzamide identified upregulated NF-κB-driven CCAAT-enhancer binding protein-β gene expression (which boosts colitogenic T-cell responses and was additionally found to be upregulated in IBD patient samples) and decreased AHR signalling. This study uses propyzamide as an example to demonstrate a pipeline for the systematic evaluation of environmental factors, which may give mechanistic insight into their colitogenic properties.
Vaccination-based immunotherapy to target profibrotic cells in liver and lung
Sobecki M, Chen J, Krzywinska E, et al. Vaccination-based immunotherapy to target profibrotic cells in liver and lung. Cell Stem Cell 2022; 29: …
Footnotes
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.