title: Innate immune defence: NOD2 and autophagy in the pathogenesis of Crohn's disease.
abstract: Crohn's disease (CD) is a chronic inflammatory disorder of the gut with a poorly understood aetiology. Epidemiological studies suggest that the disease occurs in genetically susceptible individuals as a consequence of defects in mucosal barrier function and disregulated immune recognition of commensal gut flora. Of more than 30 genetic loci associated with CD, two genes with important polymorphisms, encoding the intracellular bacterial sensor NOD2/CARD15 and the autophagic regulator ATG16L1, have gained particular prominence as they suggest an important paradigm of CD pathogenesis. Both proteins exert crucial functions in innate immune defence through intracellular bacterial recognition and destruction of bacteria. This review focuses on the physiological functions of the protein products of both genes and discusses how innate immune defences are linked to autophagic processes through recruitment of ATG16L1 by the bacterial sensor NOD2 at sites of microbial infection.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland. phruz@uhbs.ch
authors.forename: Petr
authors.initials: P
authors.lastname: Hruz
authors.forename: Lars
authors.initials: L
authors.lastname: Eckmann
mesh_terms: D001343:Autophagy / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein