Epigenetic mechanisms of epithelial – immune interactions that shape immune surveillance in the intestinal epithelium
نویسندگان
چکیده
Abstract Immune surveillance of the intestinal epithelium is regulated by reciprocal interactions between epithelial cells, immune system and microbiome. This highly specialized compartment maintains tolerance against dietary products commensal bacteria while protecting pathogens, cancer risk tissue damage. While recent studies identified epigenetic mechanisms that orchestrate self-renewal differentiation cells (IECs), little known about govern – how they influence regeneration. Here we dissect epithelial-intrinsic features including transcription factors co-activators using genetically engineered mouse models autologous human patient-derived organoid co-cultures. Ablation regulators associate with interaction gene modules specifically in IECs dampens intraepithelial lymphocyte-mediated surveillance. We precise promoter enhancer regulation both mice humans. Finally, disruption maintain lead to impaired responses clinically-relevant infection, regeneration cancer. These results establish a strong foundation towards understanding multi-cellular within barrier tissues physiology or disease states. Supported grants from Mathers Foundation, STARR Cancer Consortium (I13-0052), The Mark Foundation for Research (20-028-EDV), NIH (P30CA045508-33), CZI Ancestry Network Human Cell Atlas
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.150.04