Virus Plus Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine英文文献.pdfVIP

Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine Ken Cadwell,1 Khushbu K. Patel,1 Nicole S. Maloney,1 Ta-Chiang Liu,1 Aylwin C.Y. Ng,3,4 Chad E. Storer,5 Richard D. Head,5 Ramnik Xavier,3,4 Thaddeus S. Stappenbeck,1,* and Herbert W. Virgin1,2,6,* 1Department of Pathology and Immunology 2Department of Molecular Microbiology Washington University School of Medicine, St. Louis, MO 63110, USA 3Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA 4Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA 5Inflammation and Immunology Research Unit, Pfizer Global Research and Development, St. Louis, MO 63017, USA 6Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, St. Louis, MO 63110, USA *Correspondence: stappenb@ (T.S.S.), virgin@ (H.W.V.) DOI 10.1016/j.cell.2010.05.009 SUMMARY certain genetic backgrounds is broadly recognized. In animal models, autoimmune disease can be influenced by viral infec- It is unclear why disease occurs in only a small tions. For example, glomerulonephritis is exacerbated by lym- proportion of persons carrying common risk alleles phocytic choriomeningitis virus and polyoma virus infections in of disease susceptibility genes. Here we demon- certain inbred backgrounds (Tonietti et al., 1970), and lympho- strate that an interaction between a specific virus cytic choriomeningitis virus infection inhibits development of dia- infection and a mutation in the Crohn’s disease sus- betes in NOD mice or BB rats (Dyrberg et