biostudies-literatureConstant DAKenneth Rainin FoundationNCATS NIH HHSNIAID NIH HHS416-429https://www.ebi.ac.uk/biostudies/studies/S-EPMC10243893biostudies-literatureUnknown6(7)The three types of IFN have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated in the context of inflammatory bowel disease and may synergize with inflammatory cytokines such as TNF-α to promote tissue damage. Prior studies suggest that in mouse intestinal epithelial cells (IECs), type III IFNs are preferentially produced during viral infections and are less cytotoxic than type I IFN. In this study, we generated human IEC organoid lines from biopsies of ileum, ascending colon, and sigmoid colon of three healthy subjects to establish the baseline responses of normal human IECs to types I, II, and III IFN. We found that all IFN types elicited responses that were qualitatively consistent across intestiImmunoHorizonsTranscriptional and Cytotoxic Responses of Human Intestinal Organoids to IFN Types I, II, and III.PMC10243893T32 AI007472KRA000137UL1 TR002369R01 AI130055Constant DAVanderHoek ETsikitis VLSofia MAModiano NVan Winkle JARegner EDekker SENice TJfalseTranscriptional and Cytotoxic Responses of Human Intestinal Organoids to IFN Types I, II, and III.The three types of IFN have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated in the context of inflammatory bowel disease and may synergize with inflammatory cytokines such as TNF-α to promote tissue damage. Prior studies suggest that in mouse intestinal epithelial cells (IECs), type III IFNs are preferentially produced during viral infections and are less cytotoxic than type I IFN. In this study, we generated human IEC organoid lines from biopsies of ileum, ascending colon, and sigmoid colon of three healthy subjects to establish the baseline responses of normal human IECs to types I, II, and III IFN. We found that all IFN types elicited responses that were qualitatively consistent across intesti2022-01-01T00:00:00Z2022 Jul2026-04-08T14:18:05.557Z2025-02-19T02:38:02.163ZS-EPMC102438933579034010.4049/immunohorizons.2200025