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- Title
Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant.
- Authors
Kuballa, Petric; Huett, Alan; Rioux, John D; Daly, Mark J; Xavier, Ramnik J
- Abstract
The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn's disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn's disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn's disease. Here we report that, in human epithelial cells, the Crohn's disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn's disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy.
- Publication
PloS one, 2008, Vol 3, Issue 10, pe3391
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0003391