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Autophagy and Endoplasmic Reticulum Stress

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Crohn's Disease and Ulcerative Colitis

Abstract

Hypomorphic autophagy, a fundamental cellular catabolic process, has emerged as a key disease-specific theme associated with genetic risk for Crohn’s disease (CD), based on the original discovery of a nonsynonymous coding variation in the autophagy gene ATG16L1 and further autophagy risk genes discovered since then. Endoplasmic reticulum (ER) stress, a consequence of protein misfolding in the ER, is commonly observed in the intestinal epithelium of patients with CD and ulcerative colitis, and elicits a compensatory response, the Unfolded Protein response (UPR). Genes involved in the UPR, including XBP1, have been associated with risk for inflammatory bowel disease (IBD). The UPR and autophagy are closely intertwined, with autophagy serving a compensatory function to restrain ER stress. In vivo model systems have demonstrated that impairment of autophagy function in the context of unrestrained ER stress leads to spontaneous ileitis that closely phenocopies ileal CD and that originates from the intestinal epithelium, providing a framework on how hypomorphic autophagy may trigger disease in patients carrying the ATG16L1 T300A risk variant in the context of yet unknown environmental factors.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK

    Arthur Kaser

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  1. Arthur Kaser
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Correspondence to Arthur Kaser .

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Editors and Affiliations

  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

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Kaser, A. (2017). Autophagy and Endoplasmic Reticulum Stress. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_12

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  • DOI: https://doi.org/10.1007/978-3-319-33703-6_12

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  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-33703-6

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