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Cited by 900

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Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in Intestine

Open access
Cadwell, Ken, Patel, Khushbu K., Maloney, Nicole S., Liu, Ta-Chiang, Ng, Aylwin C.Y., Storer, Chad E., Head, Richard D., Xavier, Ramnik, Stappenbeck, Thaddeus S., Virgin, Herbert W.·2010·Cell

Abstract

SUMMARY It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn’s disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn’s disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFα and IFNγ and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease.

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Metadata

Authors
Cadwell, K., Patel, K. K., Maloney, N. S., Liu, T.-C., Ng, A. C. Y., Storer, C. E., Head, R. D., Xavier, R., Stappenbeck, T. S., & Virgin, H. W.
Venue
Cell
Publisher
Elsevier BV
Published
2010-06
Volume
141
Issue
7
Pages
1135-1145
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2153685214
Cited by
900
References
10
FWCI
49.79
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in Intestine. https://app.cochat.ai/papers/10.1016/j.cell.2010.05.009
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Cadwell, K., Patel, K. K., Maloney, N. S., Liu, T.-C., Ng, A. C. Y., Storer, C. E., Head, R. D., Xavier, R., Stappenbeck, T. S., & Virgin, H. W. (2010). Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in Intestine. Cell. https://doi.org/10.1016/j.cell.2010.05.009

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.