title: Functional defects in NOD2 signaling in experimental and human Crohn disease.
abstract: Increasing evidence suggests that a deficit in innate immunity may play a causative role in the pathogenesis of inflammatory bowel disease. The most compelling support for this hypothesis comes from the genetic association of Crohn disease (CD) with carriage of polymorphisms within the NOD2 gene, which represent the most frequent genetic defect in CD. Our findings suggest that SAMP1/YitFc mice, which develop CD-like ileitis in the absence of NOD2 genetic mutations, fail to respond to MDP administration by displaying decreased innate cytokine production and impaired bacterial clearance before the onset of disease. This provides evidence that dysregulated NOD2 signaling, genetic or functional in nature, predisposes to chronic intestinal inflammation, and supports a new paradigm that CD may occur from a deficit in innate immunity as opposed to an overly aggressive immune response. This new paradigm could lead to potential development of new preventative or therapeutic modalities for patients with CD.
authors.affiliation: Department of Medicine; Case Western Reserve University; Cleveland, OH USA; Digestive Health Research Center; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Corridoni
authors.affiliation: Department of Medicine; Case Western Reserve University; Cleveland, OH USA; Digestive Health Research Center; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Kristen O
authors.initials: KO
authors.lastname: Arseneau
authors.affiliation: Department of Medicine; Case Western Reserve University; Cleveland, OH USA; Digestive Health Research Center; Case Western Reserve University; Cleveland, OH USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000276:immunology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency*; D015398:Signal Transduction
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
keywords: Crohn disease; SAMP/YitFc; inflammatory bowel disease; innate immunity; nucleotide-binding oligomerization domain 2