{"doi":"10.1101/2025.01.04.630951","title":"Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease","abstract":"The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF–overexpressing Crohn′s disease (CD) model (Tnf ΔARE/+ ), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host′s immune susceptibility to drive region–specific disease. We identified Chlamydia muridarum , an intracellular bacterium and murine counterpart to the human sexually transmitted C. trachomatis , as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD. Disease manifestation in the AC depends on indoleamine 2,3-dioxygenase (IDO1) activity induced by hypersensitive surface secretory cells in genetically susceptible hosts. Single–cell and microbial analyses of human specimens also implicates this pathobiont–epithelial IDO1 pathway in patients with a history of CD in the AC. Our findings demonstrate that genetic and microbial factors can independently drive region–specific disease and provide a unique model to study CD specific to the AC.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559940,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":273301,"name":"Jiawei Wang","orcid":"0000-0003-2627-4897","position":1,"is_corresponding":false},{"id":722062,"name":"Erin P. 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