bioRxiv : the preprint server for biology · 2025
Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Spencer Paige N, Wang Jiawei, Smith Erin P, Spiga Luisella, Simmons Alan J, Kim Taewoo, Kim William, Brown Monica E, Yang Yilin, Kaur Harsimran, Xu Yanwen, Kang Seung Woo, Helou Matthew D, Lee Mason A, Zheng Lin, Arceneaux Deronisha, Tasneem Naila, Mueller Katherine D, Kuddar Ozge S, Harned Mariah H, Ro James, Li Jing, Banerjee Amrita, Markham Nicholas O, Wilson Keith T, Coburn Lori A, Goettel Jeremy A, Liu Qi, Kay Washington M, Valdivia Raphael H, Zhu Wenhan, Lau Ken S
Аннотация
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 (TnfΔARE/+), 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.