Murine small intestinal and colonic organoids were cultured as described previously7 (link). At day 5 (SI) or day 3 (colon) organoids were stimulated with either 500 U/ml of IFNβ (PBL Assay Science), 5 ng/ml of IL-22 (Biolegend) or left unstimulated. For RNA extraction and immunofluorescence, the organoids were stimulated for 24 or 48 h. For detection of STAT3 phosphorylation, organoids were stimulated for 2h. For human organoids, pinch biopsies were obtained from the colon of adult IBD patients undergoing surveillance colonoscopy using 2.8 mm standard biopsy forceps, after approval by the New York University School of Medicine Institutional Review Board. All tissue was isolated from non-inflamed regions of the colon. Intestinal fragments were incubated in Gentle Cell Dissociation Reagent (Stemcell Technologies) on ice for 30 minutes followed by vigorous pipetting to isolate crypts. Crypt were embedded in Corning Matrigel Growth Factor Reduced Basement Membrane Matrix (Corning), and cultured with human IntestiCult Organoid Growth Medium (Stemcell Technologies). The culture medium was changed every 2–3 days. Human organoids were stimulated with 500 U/ml IFNβ (R&D systems) or left unstimulated for 48 h.