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Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine.
- Source :
-
Cell [Cell] 2010 Jun 25; Vol. 141 (7), pp. 1135-45. - Publication Year :
- 2010
-
Abstract
- 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 TNFalpha and IFNgamma 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.
- Subjects :
- Animals
Autophagy-Related Proteins
Crohn Disease pathology
Gene Expression Profiling
Humans
Interferon-gamma metabolism
Mice
Paneth Cells metabolism
Paneth Cells virology
Tumor Necrosis Factor-alpha metabolism
Carrier Proteins genetics
Crohn Disease genetics
Crohn Disease virology
Genetic Predisposition to Disease
Ileum pathology
Norovirus
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 141
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 20602997
- Full Text :
- https://doi.org/10.1016/j.cell.2010.05.009