title: Genetically determined epithelial dysfunction and its consequences for microflora-host interactions.
abstract: The intestinal epithelium forms a highly active functional interface between the relatively sterile internal body surfaces and the enormously complex and diverse microbiota that are contained within the lumen. Genetic models that allow for manipulation of genes specifically in the intestinal epithelium have provided an avenue to understand the diverse set of pathways whereby intestinal epithelial cells (IECs) direct the immune state of the mucosa associated with homeostasis versus either productive or non-productive inflammation as occurs during enteropathogen invasion or inflammatory bowel disease (IBD), respectively. These pathways include the unfolded protein response (UPR) induced by stress in the endoplasmic reticulum (ER), autophagy, a self-cannibalistic pathway important for intracellular bacterial killing and proper Paneth cell function as well as the interrelated functions of NOD2/NF-κB signaling which also regulate autophagy induction. Multiple genes controlling these IEC pathways have been shown to be genetic risk factors for human IBD. This highlights the importance of these pathways not only for proper IEC function but also suggesting that IECs may be one of the cellular originators of organ-specific and systemic inflammation as in IBD.
authors: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ak729@cam.ac.uk
authors: Arthur
authors: A
authors: Kaser
authors: Lukas
authors: L
authors: Niederreiter
authors: Richard S
authors: RS
authors: Blumberg
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology; D020895:Enterocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D054892:Metagenome; D035683:MicroRNAs / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013312:Stress, Physiological; D056811:Unfolded Protein Response / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; D000094632:Thymic Stromal Lymphopoietin