Inflammatory Bowel Disease at the Intersection of Autophagy and Immunity: Insights from Human Genetics

  • Natalia B. Nedelsky
  • Petric Kuballa
  • Adam B. Castoreno
  • Ramnik J. Xavier


Studies using human genetics have identified more than 160 loci that affect the risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Several of these genes have been found to play key roles in the process of autophagy, a lysosome-based degradation pathway. Although historically considered to be a relatively nonselective process of degradation of cytosolic contents, autophagy has recently been revealed to have several selective and immune-specific functions that are relevant to the maintenance of intestinal homeostasis, including xenophagy, mitophagy, antigen presentation, secretion, and inflammasome regulation. In this chapter, we review the evidence that links autophagy-related genes, their immune-specific functions, and possible mechanisms of IBD pathogenesis. We summarize the basic molecular events underlying general and selective autophagy and present evidence suggesting possible pathogenic mechanisms revealed by studies of IBD-associated risk alleles of ATG16L1 and IRGM. Finally, we review chemical biology-based experimental approaches for identifying autophagy regulatory pathways that may have implications for the development of therapeutics.


Inflammatory Bowel Disease Major Histocompatibility Complex Class Paneth Cell Vesicular Trafficking Autophagic Degradation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by funding from the Crohn’s and Colitis Foundation of America and NIH grants DK043351, DK083756, and DK086502 to R.J.X.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Natalia B. Nedelsky
    • 1
  • Petric Kuballa
    • 1
    • 2
  • Adam B. Castoreno
    • 1
    • 2
  • Ramnik J. Xavier
    • 1
    • 2
  1. 1.Gastrointestinal UnitCenter for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General HospitalBostonUSA
  2. 2.Broad Institute of Harvard University and Massachusetts Institute of TechnologyCambridgeUSA

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