ArticleJournal of Crohn's & colitis2025
Eicosatetraynoic Acid Regulates Profibrotic Pathways in an Induced Pluripotent Stem Cell-Derived Macrophage-Human Intestinal Organoid Model of Crohn's Disease.
Article in Journal of Crohn's & colitis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Macrophage dysregulation in inflammatory bowel disease: cellular heterogeneity, pathogenic mechanism, and treatment.Frontiers in immunology · 2026Review
- Immune and Immune-Integrated Organoids as NextGeneration Platforms for Disease Modeling.MedComm · 2025Review
- Berberine Alleviates Intestinal Inflammation by Disrupting Pathological Macrophage-Epithelial Crosstalk in Macrophage-Organoid Co-Culture Model.International journal of molecular sciences · 2025Article
- Enteroendocrine cells regulate intestinal homeostasis and epithelial function.Molecular and cellular endocrinology · 2024Review
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Authors and funding
14 authors.
Funding
Abstract
BACKGROUND AND
aimsWe previously identified small molecules predicted to reverse an ileal gene signature for future Crohn's Disease (CD) strictures. Here we used a new human intestinal organoid (HIO) model system containing macrophages to test a lead candidate, eicosatetraynoic acid (ETYA).
methodsInduced pluripotent stem cell lines (iPSC) were derived from CD patients and differentiated into macrophages and HIOs. Macrophages and macrophage-HIO cocultures were exposed to lipopolysaccharide (LPS) with and without ETYA pretreatment. Cytospin and flow cytometry characterized macrophage morphology and activation markers, and RNA sequencing defined the global pattern of macrophage gene expression. TaqMan low-density array, Luminex multiplex assay, immunohistologic staining, and sirius red polarized light microscopy were performed to measure macrophage cytokine production and HIO profibrotic gene expression and collagen content.
resultsInduced PSC-derived macrophages exhibited morphology similar to primary macrophages and expressed inflammatory macrophage cell surface markers including CD64 and CD68. LPS-stimulated macrophages expressed a global pattern of gene expression enriched in CD ileal inflammatory macrophages and matrisome-secreted products and produced cytokines and chemokines including CCL2, IL1B, and OSM implicated in refractory disease. ETYA suppressed CD64 abundance and profibrotic gene expression pathways in LPS-stimulated macrophages. Coculture of LPS-primed macrophages with HIO led to upregulation of fibroblast activation genes including ACTA2 and COL1A1, and an increase in HIO collagen content. ETYA pretreatment prevented profibrotic effects of LPS-primed macrophages.
conclusionsETYA inhibits profibrotic effects of LPS-primed macrophages upon cocultured HIO. This model may be used in future untargeted screens for small molecules to treat refractory CD.
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