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Cited by 328

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Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's Disease Associated ATG16L1 Variant

Open access
Kuballa, Petric, Huett, Alan, Rioux, John D., Daly, Mark J., Xavier, Ramnik J.·2008·PLoS ONE

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.

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Metadata

Authors
Kuballa, P., Huett, A., Rioux, J. D., Daly, M. J., & Xavier, R. J.
Venue
PLoS ONE
Published
2008-10-13
Volume
3
Issue
10
Pages
e3391
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2116799923
Cited by
328
References
6
FWCI
21.62
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's Disease Associated ATG16L1 Variant. https://app.cochat.ai/papers/10.1371/journal.pone.0003391
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Kuballa, P., Huett, A., Rioux, J. D., Daly, M. J., & Xavier, R. J. (2008). Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's Disease Associated ATG16L1 Variant. PLoS ONE. https://doi.org/10.1371/journal.pone.0003391

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