title: Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease.
abstract: OBJECTIVE
  The purpose of this study is to provide an overview of the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in inflammatory bowel disease (IBD).
  
  
  RESULTS
  Human genetic studies have identified several UPR-related genes and autophagy-related genes as IBD risk loci. Impairment of each branch of the UPR causes spontaneous enteritis or creates higher susceptibility for intestinal inflammation in model systems. Deficiency of either UPR or autophagy in small intestinal epithelial cells promotes each other's compensatory engagement, which is especially prominent in Paneth cells such that, in the absence of both, severe spontaneous enteritis emerges.
  
  
  CONCLUSIONS
  Interactions between the UPR and autophagy exhibit critical synergistic interactions within the intestinal epithelium and especially Paneth cells that are of considerable importance to the maintenance of homeostasis. When dysfunctional in the Paneth cell, spontaneous inflammation can emerge that may extend beyond the epithelium providing direct experimental evidence that subsets of Crohn's disease may emanate from primary Paneth cell disturbances.
authors.affiliation: aDivision of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA bDivision of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hosomi
authors.forename: Arthur
authors.initials: A
authors.lastname: Kaser
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D001343:Autophagy / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D019879:Paneth Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D056811:Unfolded Protein Response / Q000235:genetics / Q000502:physiology