IL-1β Induced Intestinal Inflammation Pathogenesis in East Friesian Sheep: Insights from Organoid Modeling

Establishing an appropriate model of intestinal inflammation in vitro is crucial for studying the pathogenesis of inflammatory bowel disease (IBD). While immortalized cell lines have long been employed to investigate intestinal cell functions and host-pathogen interactions in sheep, they inadequately mimic the physiological characteristics of ovine intestinal inflammation and may lose critical genetic features. The emergence of organoids has revolutionized in vitro intestinal inflammation modeling by offering superior structural and functional fidelity to native tissues. In this study, we developed an IL-1β-induced intestinal inflammation organoid model derived from East Friesian sheep ileal crypts. Our data demonstrate that treatment with 30 ng/mL IL-1β significantly increased inflammatory factor secretion, the apoptosis of intermediate cells, and disrupted barrier integrity while simultaneously reducing bud formation capacity, organoid area, and stem cell proliferation. RNA-seq analysis revealed that IL-1β activated the NF-κB/TNF/IL-17 signaling pathway in intestinal organoids, thereby orchestrating the inflammatory response. This study establishes a novel sheep-derived intestinal inflammation organoid model, providing a physiologically relevant platform to investigate intestinal inflammation pathogenesis. These findings offer a translational tool for advancing drug development and pharmacological mechanism exploration in ovine intestinal inflammation research.